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  • 1. Ayala, Marcelo N.
    et al.
    Söderberg, Per G.
    St. Erik’s Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
    Reversal of reciprocity failure for UVR-induced cataract with vitamin E2005In: Ophthalmic Research, ISSN 0030-3747, E-ISSN 1423-0259, Vol. 37, no 3, p. 150-155Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The authors have previously described that the photochemical reciprocity law does not apply for ultraviolet radiation (UVR)-induced cataract. The aim of this study was to elucidate if failure of the reciprocity reverses with vitamin E (alpha-tocopherol) administration. METHODS: Altogether, 80 rats were divided into one group fed alpha-tocopherol and one control group. For each group, half of rats were exposed to UVR for 5 min and the remaining rats for 15 min. RESULTS: Lenses exposed to UVR for 5 min showed no difference in light scattering between alpha-tocopherol-treated and untreated groups. Lenses exposed to UVR for 15 min showed significant difference in light scattering between alpha-tocopherol-treated and untreated groups. CONCLUSIONS: Failure in exposure time-intensity reciprocity for UVR-induced cataract with exposures shorter than 30 min may be due to consumption of antioxidants in the lens.

  • 2. Ayala, Marcelo
    et al.
    Strid, Hilja
    Jacobsson, Ulrika
    Söderberg, Per G
    St. Erik's Eye Hospital, Karolinska Institutet.
    p53 expression and apoptosis in the lens after ultraviolet radiation exposure2007In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 48, no 9, p. 4187-4191Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To localize p53 protein and active caspase-3 in the albino rat lens and to compare p53 mRNA and active caspase-3 expression in ultraviolet radiation (UVR) 300 nm exposed lenses and their contralateral nonexposed controls.

    METHODS: Ten Sprague-Dawley albino rats were unilaterally exposed to 8 kJ/m(2) UVR, and the contralateral eyes were left nonexposed. In total, four exposed lenses and their respective contralateral nonexposed lenses were analyzed by immunohistochemistry to localize p53 and active caspase-3. In addition, six exposed and contralateral nonexposed lenses were analyzed by real-time RT-PCR. Quantified p53 and caspase-3 expression were compared between the in vivo UVR 300 nm exposed lenses and the contralateral nonexposed lenses.

    RESULTS: All lenses exposed to UVR developed cataract. Immunohistochemistry showed that p53 and active caspase-3 were localized in the lens epithelial cells. Quantified p53 and caspase-3 expression were significantly higher in lenses exposed to UVR than in nonexposed lenses.

    CONCLUSIONS: p53 and caspase-3 expression increase in lens epithelial cells after UVR exposure. In the lens, apoptosis induced by UVR may be associated with increased p53 expression.

  • 3. Bucht, Curry
    et al.
    Söderberg, Per G.
    St. Erik's Eye Hospital (Sweden) and Mälarsjukhuset Eskilstuna (Sweden) and Univ. of Miami.
    Manneberg, Göran
    A model for corneal endothelial morphometry by diffraction2006In: Ophthalmic Technologies XVI: Proceedings of SPIE / [ed] Fabrice Manns; Per G. Söderberg; Arthur Ho, San José, CA: SPIE , 2006, Vol. 6138, p. 6138-O-1-6138-O-8Conference paper (Refereed)
  • 4. Bucht, Curry
    et al.
    Söderberg, Per G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Manneberg, Göran
    Fully automated corneal endothelial morphometry of images captured by clinical specular microscopy2010In: Ophthalmic Technologies XX / [ed] Fabrice Manns, Per G. Söderberg, Arthur Ho, San Francisco, CA: SPIE , 2010, p. 1E-1-1E-8Conference paper (Refereed)
  • 5. Bucht, Curry
    et al.
    Söderberg, Per G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Manneberg, Göran
    Fully automated corneal endothelial morphometry of images captured by clinical specular microscopy2009In: Ophthalmic Technologies XIX / [ed] Fabrice Manns; Per G. Söderberg; Arthur Ho, San José, CA: SPIE , 2009, Vol. 7163, p. 15:1-15:8Conference paper (Refereed)
  • 6. Bucht, Curry
    et al.
    Söderberg, Per G.
    St. Erik's Eye Hospital (Sweden) and Univ. of Miami.
    Manneberg, Göran
    The impact of horizontal offset of the cornea during corneal specular microscopy2008In: Ophthalmic Technologies XVIII: Proceedings of SPIE / [ed] Fabrice Manns; Per G. Söderberg; Arthur Ho; Bruce E. Stuck; Michael Belkin, San José, CA: SPIE , 2008, Vol. 6426, p. 13-1-13-9Conference paper (Refereed)
  • 7. Bucht, Curry
    et al.
    Söderberg, Per
    St Erik's Eye Hospital (Sweden) and Univ. of Miami.
    Manneberg, Göran
    Recording the dffraction pattern reflected from corneal endothelium2007In:  Ophthalmic Technologies XVII / [ed] Fabrice Manns, Per G. Söderberg, Arthur Ho, Bruce E. Stuck, Michael Belkin, San José, CA: SPIE , 2007, Vol. 6426, p. 10:1-10:8Conference paper (Refereed)
  • 8.
    Bucht, Curry
    et al.
    S:t Eriks Ögonsjukhus, Inst. f. Neurovetenskap, KI.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Manneberg, Göran
    Biomedicinsk fysik och röntgenfysik, Inst. för tillämpad fysik.
    Simulation of specular microscopy images of corneal endothelium, a tool for control of measurement errors2011In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 89, no 3, p. e242-e250Article in journal (Refereed)
    Abstract [en]

    Purpose: We aimed at developing simulation software capable of producing images of corneal endothelium close to identical to images captured by clinical specular microscopy with defined morphometrical characteristics. It was further planned to demonstrate the usefulness of the simulator by analysing measurement errors associated with a trained operator using a commercially available semi-automatic algorithm for analysis of simulated images.

    Methods: Software was developed that allows creation of unique images of the corneal endothelium expressing morphology close to identical with that seen in images of corneal specular microscopy. Several hundred unique images of the corneal endothelium were generated with randomization, spanning a physiological range of endothelial cell density. As an example of the usefulness of the simulator for analysis of measurement errors in corneal specular microscopy, a total of 12 of all the images generated were randomly selected such that the endothelial cell density expressed was evenly distributed over the physiological range of endothelial cell density. The images were transferred to a personal computer. The imagenet-640 software was used to analyse endothelial cell size variation, percentage of hexagonal endothelial cells, and endothelial cell density.

    Results: The simulator developed allows randomized generation of corneal specular microscopy images with a preset expected average and variation of cell structure. Calculated morphometric information of each cell is stored in the simulator. The image quality can secondarily be varied with a toolbox of filters to approximate a large spectrum of clinically captured images. As an example of the use of the simulator, measurement errors associated with one trained operator using the imagenet-640 software, and focusing on endothelial cell density, were examined. The functional dependence between morphometric information estimated with the imagenet-640 software algorithm and real morphometric information as provided by the simulator was analysed with regression. It was demonstrated that that the estimations of endothelial cell size variation was associated with a scaling error and that the random error was strongly dependent on the operator.

    Conclusion: The newly developed simulator for randomized generation of morphometrically defined corneal specular microscopy images for the first time makes it possible to estimate a spatial scaling error of an available semi-automatic algorithm and to determine the random measurement error of important morphometric estimates in a defined reference sample of images. It is anticipated that the simulator will be a valuable tool for the generation of a large set of morphometrically well-characterized corneal specular microscopy images that can be used for calibration among research centres, for minimization of random errors and for measurement of quality control. Simulated images will be useful for the development of fully automatic analysis of corneal endothelial cell morphometry.

  • 9. Dong, Xiuqin
    et al.
    Löfgren, Stefan
    Ayala, Marcelo
    Söderberg, Per G
    St. Erik's Eye Hospital, Karolinska Institutet.
    Maximum tolerable dose for avoidance of cataract after repeated exposure to ultraviolet radiation in rats2007In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 84, no 1, p. 200-208Article in journal (Refereed)
    Abstract [en]

    The purpose of the present study was to determine the impact of inter-exposure interval between repeated equivalent exposures of ultraviolet radiation (UVR) on threshold accumulated dose for cataract development. Female Sprague-Dawley rats were randomly divided into 5 inter-exposure interval groups with 20 rats in each group. The inter-exposure intervals were 6 h, 1, 3, 9 and 30 days respectively. Each inter-exposure interval group was divided into 5 dose-subgroups. Only one eye of each rat was exposed to ultraviolet radiation (lambdamax=300 nm). The total dose incident on the cornea, in each subgroup varied between 0 approximately 10 kJ/m2. One week after the second exposure, the rats were sacrificed and both lenses were extracted. The intensity of forward light scattering was measured and macroscopic morphology was documented. Maximum tolerable dose (MTD) for each inter-exposure interval was estimated based on the experimentally determined dose-response function. The difference of intensity of light scattering between exposed and contralateral non-exposed lens decreased as a function of inter-exposure interval between the two equivalent exposures. The accumulated MTD2.3:16 was 5.3, 5.1, 5.4, 5.8, and 6.0 kJ/m2 UVR-B for the 6 h, 1, 3, 9 and 30 day inter-exposure interval between the two exposures, respectively. The shorter the inter-exposure interval between two subsequent exposures, the more damage. The time constant for repair of lens damage after in vivo exposure to close to threshold dose was estimated to be eight days and the fraction of repairable damage to be 20%. The accumulated threshold dose for damage after two repeated equivalent exposures to UVR-B increases as a function of inter-exposure interval up to at least 30 days inter-exposure interval.

  • 10.
    Frisk, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Mandahl, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Lönnerholm, Gudmar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Cataracts after autologous bone marrow transplantation in children2000In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 89, no 7, p. 814-819Article in journal (Refereed)
    Abstract [en]

    We recorded the incidence and degree of posterior subcapsular cataract (PSC) in 29 children who had undergone autologous (n = 28) or syngeneic (n = 1) bone marrow transplantation (BMT) due to haematologic or lymphoid malignancy. Conditioning prior to transplantation consisted either of a combination of chemotherapy and total body irradiation (TBI) (n = 21) or of chemotherapy only (n = 8). TBI was given in one fraction of 7.5 Gy. Nine patients had received previous cranial irradiation. The patients were followed for 4-10 y (median 8y) after transplantation. Of 29 patients, 22 developed PSC, all within 4 y after BMT. With the exception of one patient who developed unilateral PSC, all had received TBI. Conversely, 100% of those who received TBI developed PSC. In this group (+TBI), eight patients (38%) developed significant PSC, defined as best corrected visual acuity < 0.8 in either eye. Six patients (10 eyes) have since needed surgical repair consisting of extracapsular cataract extraction and intraocular lens implantation. There was no clear relationship between previous cranial irradiation and cataract development, nor any other obvious baseline differences between those in the +TBI group who developed significant PSC and those who did not. Although effects of previous therapy cannot be ruled out, TBI appears to be the main cause of PSC in this group of patients. Twelve patients in the +TBI group had well-preserved visual acuity throughout the study, reflecting a slow progression of PSC. This compares favourably with previous reports of allogeneic BMT, possibly owing to less need for corticosteroids after autologous BMT.

    We conclude that the incidence of PSC was high after autologous BMT where the conditioning regimen included total body irradiation.

  • 11.
    Galichanin, Konstantin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Löfgren, Stefan
    St. Erik’s Eye Hospital, Karolinska Institutet, Stockholm, Sweden .
    Bergmanson, Jan
    University of Houston College of Optometry, Houston, Texas, USA.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Evolution of damage in the lens after in vivo close to threshold exposure to UV-B radiation: cytomorphological study of apoptosis2010In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 91, no 3, p. 369-377Article in journal (Refereed)
    Abstract [en]

    The purpose of the present study was to investigate cataractogenesis and recovery of lens damage after in vivo close to threshold ultraviolet (UV)-B radiation around 300nm. Eighty six-week-old albino Sprague-Dawley rats were familiarized to a rat restrainer five days prior to exposure. Groups of non-anesthetized rats were exposed unilaterally to 8kJ/m(2) UVR-300nm. The animals were sacrificed at 1, 7, 48 and 336h following exposure. The lenses were extracted for imaging of dark-field lens macro anatomy and measurement of intensity of forward lens light scattering to quantify lens opacities. Three exposed lenses and one non-exposed lens from each time interval were examined with light and transmission electron microscopy (TEM). Macro anatomy and lens light scattering revealed that all contralateral non-exposed lenses were clear. The degree of lens opacity (difference in lens light scattering between exposed and non-exposed lenses) increased during the 336h, reaching a plateau towards the end of the observation period. Light microscopy and TEM demonstrated that apoptotic features appeared in the epithelium already 1h after UVR exposure, and small vacuoles were seen in the outer cortex. Epithelial damage occurs during the first 48h after exposure and is followed by regenerative repair at 336h post-exposure. Apoptotic epithelial cells were phagocytized by adjacent epithelial cells. Cortical fiber cells exhibited increasing damage throughout the observation period without any clear repair after 336h. In conclusion, acute UVR-induced cataract is partly a reversible. Lens epithelium is a primary target for UVR exposure. Damage to cortical fiber cells remained irreversible.

  • 12.
    Galichanin, Konstantin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Löfgren, Stefan
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Cataract after repeated daily in vivo exposure to ultraviolet radiation2014In: Health Physics, ISSN 0017-9078, E-ISSN 1538-5159, Vol. 107, no 6, p. 523-529Article in journal (Refereed)
    Abstract [en]

    Epidemiological data indicate a correlation between lifelong exposure to ultraviolet radiation and cortical cataract. However, there is no quantitative experimental data on the effect of daily repeated in vivo exposures of the eye to UVR. Therefore, this experiment was designed to verify whether the dose additivity for UVR exposures holds through periods of time up to 30 d. Eighty rats were conditioned to a rat restrainer 5 d prior to exposure. All animals were divided into four exposure period groups of 1, 3, 10, and 30 d of exposure to UVR. Each exposure period group of 20 animals was randomly divided into five cumulated UVR dose subgroups. Eighteen-wk-old non-anesthetized albino Sprague-Dawley rats were exposed daily to UVR-300 nm for 15 min. One week after the last exposure, animals were sacrificed. The lenses were extracted for macroscopic imaging of dark-field anatomy, and degree of cataract was quantified by measurement of the intensity of forward lens light scattering. Maximum tolerable dose (MTD2.3:16), a statistically defined standard for sensitivity for the threshold for UVR cataract, was estimated for each exposure period. Exposed lenses developed cataract with varying appearance on the anterior surface. Single low doses of UVR accumulated to cause cataract during periods up to 30 d. MTD2.3:16 for 1, 3, 10, and 30 d of repeated exposures was estimated to 4.70, 4.74, 4.80, and 6.00 kJ m, respectively. In conclusion, the lens sensitivity to UVR-B for 18-wk-old Sprague-Dawley rats decreases with the increasing number of days being exposed. 

  • 13.
    Galichanin, Konstantin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Svedlund, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Kinetics of GADD45a, TP53 and CASP3 gene expression in the rat lens in vivo in response to exposure to double threshold dose of UV-B radiation2012In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 97, no 1, p. 19-23Article in journal (Refereed)
    Abstract [en]

    The purpose of the present study was to investigate the evolution of expression of mRNA message for the genes for the genome stress sensor GADD45α, the apoptosis initiator TP53 and the apoptosis executor CASP3 in the rat lens in vivo in response to exposure to UVR around 300 nm. Forty six week old female albino Sprague-Dawley rats were unilaterally exposed to double threshold dose for cataract induction, 8 kJ/m2 (8.9 W/m2 for 15 min), of UVR (λmax = 300 nm). The animals were sacrificed at 1, 5, 24 and 120 h following exposure to UVR-B. For each of the GADD45α, TP53 and CASP3 genes, respectively, mRNA expression in the lenses was measured by quantitative RT-PCR. It was found that expression of mRNA for GADD45α transiently increases between 5 and 24 h after exposure. TP53 is slightly downregulated in exposed lenses at 1 and 5 h after exposure and thereafter the mRNA expression increases with a constant rate of 9.4∗10−3 rel. units/h to a 1.8 fold increase at 120 h after exposure. Expression of mRNA for CASP3 is downregulated at 1, 5 and 24 h after in vivo exposure and then increases with a constant rate of 4.7∗10−3 rel. units/h, upto a 1.3 fold upregulation at 120 h. Double threshold dose of UVR, for short delay onset of cataract, in vivo causes a transient upregulation of the stress sensor GADD45α, a concurrent downregulation of TP53 and CASP3, followed by a constant upregulation of TP53 that precedes a constant upregulation of CASP3.

  • 14.
    Galichanin, Konstantin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology. Karolinska Inst, St Eriks Eye Hosp, S-10401 Stockholm, Sweden.
    Talebizadeh, Nooshin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Characterization of Molecular Mechanisms of In vivo UVR Induced Cataract2012In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, no 69, article id e4016Article in journal (Refereed)
    Abstract [en]

    Cataract is the leading cause of blindness in the world (1). The World Health Organization defines cataract as a clouding of the lens of the eye which impedes the transfer of light. Cataract is a multi-factorial disease associated with diabetes, smoking, ultraviolet radiation (UVR), alcohol, ionizing radiation, steroids and hypertension. There is strong experimental (2-4) and epidemiological evidence (5,6) that UVR causes cataract. We developed an animal model for UVR B induced cataract in both anesthetized (7) and non-anesthetized animals (8). The only cure for cataract is surgery but this treatment is not accessible to all. It has been estimated that a delay of onset of cataract for 10 years could reduce the need for cataract surgery by 50% (9). To delay the incidence of cataract, it is needed to understand the mechanisms of cataract formation and find effective prevention strategies. Among the mechanisms for cataract development, apoptosis plays a crucial role in initiation of cataract in humans and animals (10). Our focus has recently been apoptosis in the lens as the mechanism for cataract development (8,11,12). It is anticipated that a better understanding of the effect of UVR on the apoptosis pathway will provide possibilities for discovery of new pharmaceuticals to prevent cataract. In this article, we describe how cataract can be experimentally induced by in vivo exposure to UVR-B. Further RT-PCR and immunohistochemistry are presented as tools to study molecular mechanisms of UVR-B induced cataract.

  • 15.
    Galichanin, Konstantin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Wang, Jing
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Löfgren, Stefan
    Inst. för Klinisk Neurovetenskap, Karolinska Institutet.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    A new universal rat restrainer for ophthalmic research2011In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 89, no 1, p. E67-E71Article in journal (Refereed)
    Abstract [en]

    Purpose: Immobilization of rats is required in many psychological and physiological experiments. The aim of the current paper was to invent a universal device allowing for adaptation of rats of a wide age range and to maximize convenience for in vivo exposure to optical radiation under not-anaesthetized conditions.

    Methods: Eighty-three 6-week-old and three 18-week-old Sprague-Dawley albino female rats were progressively familiarized daily with the restraining device 5 days prior to exposure to acquire a conditioned response and to reduce stress. After initial habituation, 10 min preceding the ultraviolet radiation (UVR) exposure, the animal was fixed in the rat restrainer. Each unanaesthetized animal was unilaterally exposed to a single dose of 8 kJ/m(2) UVR-300 nm for 15 min. Three of the 6-week-old and three of the 18-week-old rats were in vivo exposed to UVR once for 10 consecutive days.

    Results: All rats acclimatized well to immobilization in the restrainer. Young rats adapted quicker than older rats. The device prevented head movement and body rotation, which allowed for uncomplicated single as well as repeated in vivo exposures to UVR.

    Conclusions: The restrainer effectively immobilizes unanaesthetized rats in the age range 6-18 weeks old, making it useful in future projects involving chronic repeated in vivo exposure of the eye to UVR.

  • 16.
    Galichanin, Konstantin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Yu, Zhaohua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Upregulation of GADD45a, TP53 and CASP3 mRNA expression in the rat lens after in vivo exposure to sub-threshold exposure to UVR B2014In: Journal of Ocular Biology, ISSN 2334-2838, Vol. 2, no 1, p. 5-Article in journal (Refereed)
    Abstract [en]

    Purpose:

    The objective of the present study was to investigate the evolution of mRNA expression of the stress sensor GADD45α, the apoptosis initiator TP53 and the apoptosis executor CASP3 in the rat lens after in vivo exposure to sub-threshold dose of UVR-B.

    Methods:

    Forty six-week-old female albino Sprague-Dawley rats were unilaterally exposed to a sub-threshold dose, 1 kJ/m2 (1.1 W/m2 for 15 min), of UVR (λmax = 300 nm). Anesthetized and dilated eyes were exposed to UVB radiation. The animals were sacrificed at 1, 5, 24 and 120 h post-exposure. mRNA expression of the GADD45α, TP53 and CASP3 genes in the lenses was measured by quantitative RT‑PCR, and fold change in mRNA expression between exposed and unexposed lenses was calculated.

    Results:

    mRNA expression for GADD45α increased to a 1.2 fold change at 1 h after exposure and then returned to no change at 120 h. mRNA expression for TP53 increased with a regression coefficient of 0.04 h-1 to a maximum of 1.67 fold change. mRNA expression for CASP3 increased with a regression coefficient of 4.5 x10-3 rel. units/h to a 1.46 fold change at 120 h after exposure.

    Conclusions:

    A sub-threshold in vivo exposure to UVR-B causes a transient upregulation of the stress sensor GADD45α at 1 h after exposure, a saturating upregulation of TP53 and a subsequent constant upregulation of CASP3 in the rat lens.

  • 17.
    ICNIRP, Org
    et al.
    International Commission for Non-Ionizing Radiation Protection.
    Green, Adele
    Coggon, David
    de Seze, René
    Gowland, Penny
    Marino, Carmela
    Peralta, Agnes
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Stam, Rianne
    Ziskini, Marwin
    van Rongen, Eric
    Feychting, Maria
    Assmus, Monica
    Croft, Rodney
    D'Inzeo, Giorgio
    Hirata, Akimasa
    Miller, Sharon
    Oftedal, Gunhild
    Okuno, Tsuboto
    Röösli, Martin
    Sienkiewicz, Zenon
    Watanabe, Soichi
    Diagnostic devices using static magnetic fields and non-ionising radiation (NIR): Existing regulations and potential health risks2017In: Health physics, ISSN 0017-9078, Vol. 112, p. 305-321Article in journal (Refereed)
  • 18. International Commission on Non-Ionizing Radiation Protection,
    Guidelines on limits of exposure to incoherent visible and infrared radiation2013In: Health Physics, ISSN 0017-9078, E-ISSN 1538-5159, Vol. 105, no 1, p. 74-96Article in journal (Refereed)
    Abstract [en]

    Guidelines for exposure to visible and infrared radiation were first proposed by ICNIRP in 1997. Related guidelines on limits of exposure to ultraviolet radiation (UVR) and laser radiation have been published. This document presents a revision of the guidelines for broadband incoherent radiation.

  • 19. International Commission on Non-Ionizing Radiation Protection,
    Guidelines on limits of exposure to laser radiation of wavelengths between 180 and 1000 um2013In: Health Physics, ISSN 0017-9078, E-ISSN 1538-5159, Vol. 105, no 3, p. 271-295Article in journal (Refereed)
    Abstract [en]

    Since the publication of the ICNIRP Revision of the Guidelines on Limits of Exposure to Laser Radiation (ICNIRP 1996, 2000), further research supports amending the retinal thermal exposure limits in terms of spot size dependence, pulse duration dependence for short pulses and wavelength dependence between 1,200 nm and 1,400 nm. A detailed discussion of the rational for the changes is presented in the Appendix of these Guidelines (Rationale for updating the Guidelines).

  • 20.
    Kronschläger, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Forsman, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Yu, Zhaohua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Talebizadeh, Nooshin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Löfgren, Stefan
    Meyer, Linda M
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Pharmacokinetics for topically applied caffeine in the rat2014In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 122, p. 94-101Article in journal (Refereed)
    Abstract [en]

    Topically applied caffeine was recently identified as a promising candidate molecule for cataract prevention. Little is known about the pharmacokinetics for topically applied caffeine. Potential toxicity of 72 mM caffeine on the ocular surface and the lens was qualitatively monitored and no toxic effects were observed. The concentration of caffeine was measured in the lens and the blood after topical application of 72 mM caffeine to groups of 10 animals sacrificed at 30, 60, 90 and 120 min after topical application. The lens concentration decreased throughout the observation period while the blood concentration increased up to 120 min. Further, the concentration of caffeine in the lens and blood was measured 30 min after topical application of caffeine, the concentration of caffeine being 0.72, 3.34, 15.51 and 72 mM depending on group belonging, in groups of 10 animals. The caffeine concentration in lens and blood, respectively, increased proportionally to the caffeine concentration topically applied. The rat blood concentrations achieved were far below the equivalent threshold dose of FDA recommended daily dose for humans. This information is important for further development of caffeine eye drops for cataract prevention.

  • 21.
    Kronschläger, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Galichanin, Konstantin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Ekström, Joakim
    Dept. of Statistics, UCLA.
    Lou, Marjorie
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Protective Effect of The Thioltransferase Gene On In Vivo UVR-300 nm Induced Cataract: In vivo protection of Grx1 against UVR in the lens2012In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 53, no 1, p. 248-252Article in journal (Refereed)
    Abstract [en]

    Purpose. To determine the protection factor (PF) for glutaredoxin-1 (Grx1) with regard to UVR-induced cataract by comparison of in vivo ultraviolet radiation (UVR) lens toxicity between double knockout Grx1−/− and Grx1+/+ mice.

    Methods. Twenty Grx1+/+ mice and 20 Grx1/ mice were unilaterally exposed in vivo to UVR for 15 minutes. Groups of four animals each received 0.0, 2.1, 2.9, 3.6, and 4.1 kJ/m2 UVR-300 nm. At 48 hours after UVR exposure, light-scattering in the exposed and contralateral nonexposed lenses was measured quantitatively. Macroscopic lens changes were documented with dark-field illumination photography.

    Results. UVR-300 nm induced subcapsular and cortical cataract in Grx1−/− and Grx1+/+ mice. In both Grx1−/− and Grx1+/+, the light-scattering intensified with increased in vivo exposure doses of UVR-300 nm. The intensity of forward light-scattering was higher in the lenses of Grx1−/− mice than in the lenses of Grx1+/+ mice. The threshold dose for in vivo UVR-300 nm–induced cataract, expressed as MTD2.3:16, was 3.8 in the Grx1+/+ group and 3.0 in the Grx1−/− group, resulting in a PF of 1.3.

    Conclusions. The PF is an objective relative measure of protective properties. The Grx1 gene is associated with an in vivo PF of 1.3. This result signifies that the presence of the gene allows a 1.3 times longer in vivo exposure to UVR, at equivalent irradiance, than the absence of the gene before early-onset, UVR-induced cataract occurs. This finding indicates the important role of the Grx1 gene in the oxidation defense system of the lens.

  • 22.
    Kronschläger, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Lofgren, Stefan
    Yu, Zhaohua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Talebizadeh, Nooshin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Varma, Shambhu D.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Caffeine eye drops protect against UV-B cataract2013In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 113, p. 26-31Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to investigate if topically applied caffeine protects against in vivo ultraviolet radiation cataract and if so, to estimate the protection factor. Three experiments were carried out. First, two groups of Sprague-Dawley rats were pre-treated with a single application of either placebo or caffeine eye drops in both eyes. All animals were then unilaterally exposed in vivo to 8 kJ/m(2) UV-B radiation for 15 min. One week later, the lens GSH levels were measured and the degree of cataract was quantified by measurement of in vitro lens light scattering. In the second experiment, placebo and caffeine pre-treated rats were divided in five UV-B radiation dose groups, receiving 0.0, 2.6, 3.7, 4.5 or 5.2 kJ/m(2) UV-B radiation in one eye. Lens light scattering was determined after one week. In the third experiment, placebo and caffeine pre-treated rats were UV-B-exposed and the presence of activated caspase-3 was visualized by immunohistochemistry. There was significantly less UV-B radiation cataract in the caffeine group than in the placebo group (95% confidence interval for mean difference in lens light scattering between the groups = 0.10 +/- 0.05 tEDC), and the protection factor for caffeine was 1.23. There was no difference in GSH levels between the placebo- and the caffeine group. There was more caspase-3 staining in UV-B-exposed lenses from the placebo group than in UV-B-exposed lenses from the caffeine group. Topically applied caffeine protects against ultraviolet radiation cataract, reducing lens sensitivity 1.23 times.

  • 23.
    Kronschläger, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Yu, Zhaohua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Talebizadeh, Nooshin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Meyer, Linda M.
    Hallböök, Finn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience.
    Söderberg, Per G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Evolution of TUNEL-labeling in the Rat Lens After In Vivo Exposure to Just Above Threshold Dose UVB2013In: Current Eye Research, ISSN 0271-3683, E-ISSN 1460-2202, Vol. 38, no 8, p. 880-885Article in journal (Refereed)
    Abstract [en]

    Purpose/Aim:

    To quantitatively analyse the evolution of TUNEL-labeling, after in vivo exposure to UVB.

    Methods:

    Altogether, 16 Sprague Dawley rats were unilaterally exposed in vivo for 15 min to close to threshold dose, 5 kJ/m(2), of ultraviolet radiation in the 300nm wavelength region. Animals were sacrificed in groups of 4 at 1, 5, 24 and 120 h after exposure. For each animal, both eye globes were removed and frozen. The frozen eye was cryo-sectioned in 10 mm thick midsagittal sections. From each globe, three midsagittal sections with at least five sections interval in between were mounted on a microscope slide. Sections were TUNEL-labeled and counter stained with DAPI. For quantification of apoptosis, a fluorescence microscope was used. In sections with a continuous epithelial cell surface, the number of lens epithelial cell nuclei and the number of TUNEL-positive epithelial cell nuclei was counted. The total number of TUNEL-positive epithelial cell nuclei for all three sections of one lens in relation to the total number of epithelial cell nuclei for all three sections of the same lens was compared between exposed and contralateral not exposed lens for each animal.

    Results:

    The relative difference of the fraction of TUNEL-positive nuclei between exposed and contralateral not exposed lens increased gradually, peaked in the time interval 5-120 h after exposure, and then declined.

    Conclusions:

    Close to threshold dose of UVB induces TUNEL-labeling that peaks in the time window 5-120 h after exposure to UVB.

  • 24.
    Kronschläger, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Yu, Zhaohua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Talebizadeh, Nooshin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Meyer, Linda Maren
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Topically applied caffeine induces miosis in the ketamine/xylazine anesthetized rat2014In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 127, p. 179-183Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to examine if topically applied caffeine influences pupil size in ketamine/xylazine anesthetized animals. Two experiments were carried out. In the first experiment, caffeine was topically applied to one of the eyes of 10 ketamine/xylazine anesthetized animals, while vehicle only was topically applied to the contralateral eye. In the second experiment, caffeine was topically applied to both eyes in one group of 10 ketamine/xylazine anesthetized rats, while in another group both eyes vehicle only was topically applied to both eyes. In both experiments pupil diameter was measured at 0, 10, 20, 40 and 60 min after topical application. In three of the animals, the pupil was dilated with tropicamide 5 mg/ml at 60 min after the topical application of caffeine and the pupil diameter was measured. The first experiment showed a relative miosis in caffeine treated eyes as compared to the vehicle treated eye, that changed over time. The second experiment in line with the first experiment, also showed that topically applied caffeine causes a relative miosis as compared to vehicle only that changes over time. Eyes treated with caffeine reacted with quick dilatation after tropicamide application. Topical caffeine antagonizes ketamine/xylazine anesthesia induced mydriasis in a time dependent manner.

  • 25. Lee, Richard
    et al.
    Cuthbertson, Fiona M
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Liu, Christopher
    A possible strategy for implanting blue-blocking intraocular lenses2012In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 90, no 2, p. e151-Article in journal (Refereed)
  • 26.
    Löfgren, Stefan
    et al.
    Inst. för Klinisk Neurovetenskap, Karolinska Institutet.
    Michael, Ralph
    Barraquer Institute.
    Söderberg, Per G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Impact of iris pigment and pupil size in ultraviolet radiation cataract in rat2012In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 90, no 1, p. 44-48Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the effect of iris pigment and pupil size in ultraviolet radiation (UVR)-induced cataract.

    Methods: Brown-Norway rats (pigmented) and Fischer-344 rats (non-pigmented) were unilaterally exposed in vivo to 5 kJ/m(2) UVR. Each strain was split into two groups, each receiving either mydriatic (tropicamide) or miotic (pilocarpine) eye-drops. One week after exposure, the degree of ocular inflammation and damage in the anterior segment was determined. The lenses were extracted, photographed and the degree of forward light scattering (cataract) was quantified.

    Results: The cataract types differed between the two strains. All Fischer rats developed macroscopically identifiable UVR cataract while only 41% of Brown-Norway rats did so. All groups except the miotic Brown-Norway developed significant light scattering. The Fischer rats developed 3-4-fold more lens light scattering than the Brown-Norway rats. The miotic Fischer group exhibited significantly more light scattering than the mydriatic Fischer group. There was no significant difference in light scattering between the two Brown-Norway groups. There was a correlation between ocular inflammation and degree of light scattering, with Brown-Norway rats exhibiting less inflammation and lens light scattering.

    Conclusions: Pigmented rats develop less UVR cataract and less ocular inflammation than non-pigmented rats. Pupil size plays a smaller role in UVR cataract development in pigmented rats than in non-pigmented. The role of UVR-induced ocular inflammation in cataract development is still ambiguous.

  • 27.
    Malmberg, Filip
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Sandberg-Melin, Camilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology. Center for Research and Development, Region Gävleborg.
    Söderberg, Per G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Estimating a structural bottle neck for eye–brain transfer of visual information from 3D-volumes of the optic nerve head from a commercial OCT device2016In: Ophthalmic Technologies XXVI, Bellingham, WA: SPIE - International Society for Optical Engineering, 2016, article id 96930NConference paper (Refereed)
  • 28.
    Malmqvist, Lars D.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Söderberg, Per G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    The Uppsala Contrast Sensitivity Test (UCST) - A fast strategy for clinical assessment of spectral contrast sensitivity2014In: Ophthalmic Technologies XXIV, 2014, p. 89300H-Conference paper (Refereed)
    Abstract [en]

    Routine clinical measurement of spectral contrast sensitivity is hampered by the time consumption of current methods. We are developing a system that allows instantaneous measurement of spectral contrast sensitivity. The UCST system consists of custom software running on an iPad connected to a calibrated TFT-monitor. Twenty healthy subjects were consecutively randomized to have their spectral contrast sensitivity measured with the UCST strategy or with a Vistech VCTS 6500 chart. The examination time and the spectral contrast sensitivity, respectively, were recorded for each eye in each subject. The Vistech strategy resulted in a more extended mean examination time (CI- Vistech: mu (0.95) = 87 +/- 27 s, d.f. = 9) than the UCST strategy (CI- UCST: mu (0.95) = 13 +/- 4 s, d.f. = 9), and the estimated mean difference between the two strategies indicated a difference in examination time (CI- difference: mu (0.95) = [47; 106] s, d.f. = 18). The overall contrast sensitivity for each group was estimated as the contrast sensitivities for the spatial frequencies sampled, integrated over the spatial frequency band sampled. The Vistech strategy resulted in a higher estimated mean overall contrast sensitivity (CI-Vistech: mu (0.95) = 116 +/- 24 log rel. log [c. deg(-1)], d.f. = 9) than the UCST strategy (CIUCST: mu (0.95) = 74 +/- 14 log rel. log [c. deg(-1)], d.f. = 9), and the estimated mean difference between the two strategies indicated a difference in overall contrast sensitivity (CI-difference: mu (0.95) = [15; 68] log rel. log [c. deg(-1)]), d.f. = 18). It is concluded that the UCST strategy measures spectral contrast sensitivity on the order of 7 times faster than the Vistech strategy. The slightly lower overall contrast sensitivity recorded for the UCST strategy appeared to be due to a limitation in dynamic range that can be overcome with improved design.

  • 29.
    Manns, Fabrice
    et al.
    Bascom Palmer Eye Institute, Miami University.
    Söderberg, PerUppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.Ho, ArthurInstitute for Eye Research, Ltd, Australia .
    Ophthalmic Technologies XXI2011Conference proceedings (editor) (Refereed)
  • 30.
    Manns, Manns
    et al.
    Bascom Palmer Eye Institute, University of Miami, FL, USA .
    Ho, ArthurBrian Holden Vision Institute, Sidney, Australia.Söderberg, PerUppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Ophthalmic Technologies XXII2012Conference proceedings (editor) (Refereed)
  • 31. Manns, Manns
    et al.
    Ho, ArthurSöderberg, PerUppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Ophthalmic Technologies XXIII2013Conference proceedings (editor) (Refereed)
  • 32.
    Manns, Manns
    et al.
    University of Miami, Dept. of Biomedical Engineering, FL, USA.
    Ho, ArthurBrien Holden Vision Institute, Australia.Söderberg, PerUppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Ophthalmic Technologies XXIX2019Conference proceedings (editor) (Refereed)
  • 33.
    Manns, Manns
    et al.
    University of Miami, Dept. of Biomedical Engineering.
    Ho, ArthurSöderberg, PerUppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Ophthalmic Technologies XXVII2017Conference proceedings (editor) (Refereed)
  • 34.
    Manns, Manns
    et al.
    Deprtment of Biomedical Engineering, University of Miami, FL.
    Söderberg, PerUppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.Ho, ArthurBrian Holden Vision Institue, Sidney University.
    Ophthalmic Technologies XXIV2014Conference proceedings (editor) (Refereed)
  • 35.
    Manns, Manns
    et al.
    University of Miami, Dept. of Biomedical Engineering.
    Söderberg, PerUppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.Ho, Arthur
    Ophthalmic Technologies XXV2015Conference proceedings (editor) (Refereed)
  • 36. Manns, Manns
    et al.
    Söderberg, PerUppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.Ho, Arthur
    Ophthalmic Technologies XXVI2016Conference proceedings (editor) (Refereed)
  • 37.
    Manns, Manns
    et al.
    University of Miami, Dept. of Biomedical Engineering.
    Söderberg, PerUppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.Ho, Arthur
    Ophthalmic Technologies XXVIII2018Conference proceedings (editor) (Refereed)
  • 38.
    Mathew, Jessica
    et al.
    College of Optometry, University of Houston.
    Goosey, John
    Houston Eye Associates, Houston, Texas, USA.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Bergmanson, Jan
    College of Optometry, University of Houston.
    Lamellar changes in the keratoconic cornea2015In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 93, no 8, p. 767-773Article in journal (Refereed)
  • 39. McKinlay, A F
    et al.
    Bernhardt, J H
    Ahlbom, A
    Cesarini, J P
    de Gruijl, F R
    Hietanen, M
    Owen, R
    Sliney, D H
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Swerdlow, A J
    Taki, M
    Tenforde, T S
    Vecchia, P
    Veyret, B
    Matthes, R
    Repacholi, M H
    Diffey, B
    Mainster, M A
    Okuno, T
    Stuck, B E
    Guidelines on limits of exposure to ultraviolet radiation of wavelengths between 180 nm and 400 nm (incoherent optical radiation)2004In: Health Physics, ISSN 0017-9078, E-ISSN 1538-5159, Vol. 87, no 2, p. 171-186Article, review/survey (Refereed)
  • 40. Meyer, Linda M.
    et al.
    Dong, Xiuqin
    Wegener, Alfred
    Söderberg, Per
    St. Erik's Eye Hospital, Karolinska Institutet.
    Dose dependent cataractogenesis and Maximum Tolerable Dose (MTD(2.3:16)) for UVR 300 nm-induced cataract in C57BL/6J mice2008In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 86, no 2, p. 282-289Article in journal (Refereed)
    Abstract [en]

    The purpose of the present study was to investigate the in vivo dose response function for UVR 300 nm-induced cataract in the C57BL/6J mouse lens and to establish a cataract threshold estimate expressed as Maximum Tolerable Dose (MTD(2.3:16)) for UVR 300 nm-induced cataract in the C57BL/6J mouse lens. Knowledge of the MTD(2.3:16) in the C57BL/6J mouse will permit quantitative in vivo comparison of UVR-B threshold sensitivity of knockout mice, e.g. animals deficient in key antioxidative enzymes or mice suffering from genetically predetermined eye disease, to wild type animals. Eighty C57BL/6J mice were divided into four dose groups. The animals were exposed unilaterally to 0, 2, 4, or 8 kJ/m(2) UVR 300 nm for 15 min (n=20). The radiation output of the UVR-source had lambda(max) at 302.6 nm with 5 nm full width at half maximum. Two days after exposure cataract was quantified as forward lens light scattering intensity in the exposed and the contralateral non-exposed lens. Morphological lens changes were documented using grid and dark field illumination photography. MTD(2.3:16) was estimated from the forward light scattering measurements. Two days after exposure mainly anterior subcapsular but also cortical and nuclear cataract developed in lenses that had received 2, 4, and 8 kJ/m(2) UVR 300 nm. Forward light scattering intensity increased with increasing UVR 300 nm dose. MTD(2.3:16) for the mouse lens was estimated to 2.9 kJ/m(2) UVR 300 nm. Lens light scattering intensity in the C57BL/6J mouse lens increases with UVR 300 nm in vivo dose in the range 0-8 kJ/m(2). The MTD(2.3:16) of 2.9 kJ/m(2) in the C57BL/6J mouse lens determined here, is essential to quantify and compare in vivo the impact of genetic modulation on lens susceptibility to oxidative stress and plan dose-ranges in future investigations of UVR 300 nm-induced cataract pathogenesis.

  • 41. Meyer, Linda M.
    et al.
    Dong, Xiuqin
    Wegener, Alfred
    Söderberg, Per
    St Erik's Eye Hospital, Karolinska Institute, Stockholm, Sweden.
    Light scattering in the C57BL/6 mouse lens2007In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 85, no 2, p. 178-182Article in journal (Refereed)
    Abstract [en]

    PURPOSE

    To characterize inherent light scattering in the C57BL/6 mouse lens.

    METHODS

    Lenses from 20 6-week-old female C57BL/6 mice were extracted from freshly enucleated globes and microsurgically cleaned of remnants of the ciliary body. Lens light scattering was measured quantitatively with a light dissemination meter (LDM). Morphological properties of the mouse lenses were documented using grid- and dark-field illumination photography. Analysis of variance was performed to establish variance for animals, variance between left and right eyes and variance for measurements.

    RESULTS

    Average inherent light scattering in the C57BL/6 mouse lens is 0.16 +/- 0.02 tEDC (transformed equivalent diazepam concentration). The mean size of a mouse lens at 6 weeks is 1.9 mm in diameter. Two lenses featured pre-existing cortical lens opacities. Variance for animals was assessed to be 7.9 10(- 4) tEDC(2), variance for measurements was 1.6 10(- 4) tEDC(2), and variance between left and right eyes was 8.8 10(- 4) tEDC(2). The tolerance limit for non-pathological light scattering was determined to 0.26 tEDC. No significant difference in light scattering between left and right mouse lenses was found. The minimum number of C57BL/6 mice required for detection of a 10% experimentally induced change in light scattering intensity was estimated to be 50 for independent group experiments and 25 for paired design experiments.

    CONCLUSIONS

    The C57BL/6 mouse is a suitable animal in which to conduct experiments on light scattering or cataractogenesis with high precision at reasonable sample sizes. Before including C57BL/6 mice into a study on cataractogenesis, pre-existing lens opacities such as congenital cataract must be excluded.

  • 42. Meyer, Linda M
    et al.
    Löfgren, Stefan
    St. Erik's Eye Hospital, Karolinska Institutet.
    Ho, Ye-Shih
    Lou, Marjorie
    Wegener, Alfred
    Holz, Frank
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Absence of glutaredoxin1 increases lens susceptibility to oxidative stress induced by UVR-B2009In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 89, no 6, p. 833-839Article in journal (Refereed)
    Abstract [en]

    We investigated if the absence of glutaredoxin1, a critical protein thiol repair enzyme, increases lens susceptibility to oxidative stress caused by in vivo exposure to ultraviolet radiation type B (UVR-B). Glrx(-/-) mice and Glrx(+/+) mice were unilaterally exposed in vivo to UVR-B for 15 min. Groups of 12 animals each received 4.3, 8.7, and 14.5 kJ/m(2) respectively. 48 h post UVR-B exposure, the induced cataract was quantified as forward lens light scattering. Cataract morphology was documented with darkfield illumination photography. Glutathione (GSH/GSSG) content was analyzed in Glrx(-/-) and Glrx(+/+) lenses. UVR-B exposure induced anterior sub-capsular cataract (ASC) in Glrx(-/-) and Glrx(+/+) mice. In Glrx(-/-) lenses the opacities extended further towards the lens equator than in wild type animals (Glrx(+/+)). Lens light scattering in Glrx(-/-) mice was increased in all dose groups compared to lenses with normal glutaredoxin1 function. The difference was more pronounced with increasing exposure dose. Lens sensitivity for UVR-B induced damage was significantly higher in Glrx(-/-) lenses compared to Glrx(+/+) lenses. The Glrx gene provides a 44% increase of protection against close to threshold UVR-B induced oxidative stress compared to the absence of the Glrx gene. In conclusion, the absence of glutaredoxin1 increases lens susceptibility to UVR-B induced oxidative stress in the mouse.

  • 43. Meyer, Linda M
    et al.
    Löfgren, Stefan
    Holz, Frank G
    Wegener, Alfred
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Bilateral cataract induced by unilateral UVR-B exposure: evidence for an inflammatory response2013In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 91, no 3, p. 236-242Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate whether unilateral in vivo UVR-B exposure of one eye affects the fellow eye in a co-cataractogenic, sympathetic reaction and to determine whether an inflammatory response could be involved in the pathogenesis.

    Methods: C57BL/6 mice were unilaterally exposed in vivo to UVR-B for 15 min. In the group of 24 animals each received 0×/2×/3×/or 4× cataract threshold equivalent dose. Following 48-hr UVR-B exposure, cataract morphology was documented in dark-field illumination photography, and light scattering was quantified, in both lenses in vitro. Serum levels of pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α were analysed with ELISA. Immunohistochemistry was performed for inflammatory infiltration in exposed and contralateral eyes.

    Results: UVR-B exposure induced cataract in all exposed lenses. There was additionally a significant UVR dose-dependent increase in light scattering in the lenses of the non-exposed fellow eye. Inflammatory infiltration was detected immunohistochemically in the anterior segment of both eyes. IL-1β serum concentration increased with increasing UVR-B exposure dose. There was a similar trend for serum IL-6 but not for TNF-α.

    Conclusion: Unilateral UVR-B exposure to one eye is associated with intraocular inflammation and an increase in lens light scattering also in the unexposed, fellow eye. A resulting systemic inflammatory response might be mediated by IL-1β and possibly IL-6. The finding that an inflammatory response may play a role in UVR-B-induced cataract development might initiate new strategies in the prevention of the disease.

  • 44. Meyer, Linda M.
    et al.
    Söderberg, Per
    St Erik's Eye Hospital, Karolinska Institutet.
    Dong, Xiuqin
    Wegener, Alfred
    UVR-B induced cataract development in C57 mice2005In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 81, no 4, p. 389-394Article in journal (Refereed)
    Abstract [en]

    The evolution of the morphological appearance and intensity of light scattering in C57 mice lenses after exposure to ultraviolet radiation type B (UVR-B) was investigated. A total of 80, 6-week-old female C57BL/6 mice were divided into four groups (n=20). One eye in each animal was exposed in vivo to UVR-B in the 300 nm wavelength region (UVR-B-300 nm) to a dose of 5 kJm(-2) for 15 min. The radiation output had lambda(max) at 302 nm with 5 nm [FWHM]. The animals were consecutively sacrificed at 1, 2, 4 and 8 days after the exposure. Macroscopic lens changes were documented using grid- and dark field illumination photography. Light scattering in the exposed and contralateral not exposed lens was measured quantitatively. Morphological lens changes were documented using grid- and dark field illumination photography. In vivo exposure to UVR-B-300 nm induced subcapsular cataract in all exposed lenses and occasionally cortical and nuclear cataract at all investigated time points. Exposed lenses scattered light significantly higher on all investigated days compared to contralateral non-exposed lenses. A transient increase of light scattering peaking at day 2 in exposed as well as in contralateral not exposed lenses was identified. Light scattering of the lenses varies with latency time after exposure. A dose of 5 kJm(-2) UVR-B-300 nm induces light scattering in C57 mice lenses. The increase has a transient peak at 2 days after exposure. The variation of light scattering among days 1, 2, 4, and 8 indicates a dynamic change of scattering characteristics in the mouse lens following unilateral in vivo exposure to 5 kJm(-2) UVR-B-300 nm.

  • 45.
    Meyer, Linda
    et al.
    Herzog Carl Theodor Eye Clinic, Munich, Germany.
    Wegener, Alfred
    University Eye Clinic Bonn, Bonn, Germany.
    Holzt, Frank
    University Eye Clinic Bonn, Bonn, Germany.
    Kronschläger, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Bergmanson, Jan
    University of Houston, College of Optometry, Houston, TX, USA.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Ultrastructure of UVR-B-induced cataract and repair visualized with electron microscopy2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 7, p. 635-643Article in journal (Refereed)
    Abstract [en]

    Purpose

    The aim of the study is to investigate and visualize the ultrastructure of cataract morphology and repair, after in vivo exposure to double threshold dose UVR-B in the C57BL/6 mouse lens.

    Methods

    Twenty-six-week-old C57BL/6 mice received in vivo double threshold dose (6.4 kJ/m2) UVR-B for 15 min. The radiation output of the UVR-source had λMAX at 302.6 nm. After a latency period of 1, 2, 4 and 8 days following UVR-B exposure, the induced cataract was visualized with electron microscopy techniques. Induced, cataract was quantified as forward lens light scattering. Damage to the lens epithelium and the anterior cortex was investigated with light microscopy in toluidine blue-stained semi-thin sections, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and dark field illumination photography.

    Results

    UVR-B-exposed lenses developed anterior subcapsular and/or cortical and nuclear cataract after 1 day. Lens light scattering peaked 2 days after exposure. Lens epithelial cell damage was seen in TEM as apoptotic cells, apoptotic bodies, nuclear chromatin condensation, and swollen and disrupted anterior cortex fibres throughout the sections of the whole anterior lens surface. These morphologic changes were also visualized with SEM. Within 8 days, anterior subcapsular cataract was repaired towards the anterior sutures.

    Conclusion

    UVR-B exposure of double cataract threshold dose induces a subtotal loss of epithelial cells across the whole anterior surface of the lens. This damage to the epithelium is repaired by epithelial cell movement from the equator towards the lens sutures, thus in retrograde direction to regular epithelial cell differentiation.

  • 46.
    Mody Jr, Vino C
    et al.
    S:t Eriks Ögonsjukhs, Inst. f. neurovetenskap, KI.
    Kakar, Manoj
    S:t Eriks Ögonsjukhs, Inst. f. neurovetenskap, KI.
    Söderberg, Per G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Löfgren, Stefan
    S:t Eriks Ögonsjukhus, Inst. för Neurovetenskap, KI.
    High lenticular tolerance to ultraviolet radiation-B by pigmented guinea-pig: application of a safety limit strategy for UVR-induced cataract2012In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 90, no 3, p. 226-230Article in journal (Refereed)
    Abstract [en]

    Purpose: The purpose of this study was to determine a threshold measure, maximum tolerable dose (MTD), for avoidance of UVR-B-induced cataract in the pigmented guinea-pig.

    Methods: Thirty pupil-dilated anesthetized young female guinea-pigs, divided into five equal groups, received between 0 and 84.9 kJ/m(2) unilateral UVR-B. Lens extraction and in vitro lens photography occurred 24 hr after exposure. Measurement of intensity of lens light scattering served as quantifying tool for the degree of cataract. Data analysis included regression, using a second order polynomial model. The applied MTD concept was based on the UVR-B dose-response curve obtained for the pigmented guinea-pig. A smaller number of pigmented guinea-pigs, pigmented rats and albino rats underwent morphometric analysis of the anterior segment geometry.

    Results: All eyes exposed to UVR-B developed cataract in the anterior subcapsular region. MTD for avoidance of UVR-B-induced cataract was 69.0 kJ/m(2) in the pigmented guinea-pig. Iris was considerably thicker in the guinea-pig than in the rats. Lens blockage by the dilated iris was lowest in the guinea-pig.

    Conclusions: Maximum tolerable dose for avoidance of UVR-B-induced cataract in the pigmented guinea-pig was 69.0 kJ/m(2), over 10-fold higher than the threshold 5 kJ/m(2) obtained by Pitts et al. in the pigmented rabbit. Maximum tolerable dose is an appropriate method for estimation of toxicity for UVR-B-induced cataract in the guinea-pig. The pigmented guinea-pig is significantly less sensitive to UVR-B exposure than the pigmented rabbit and pigmented rat.

  • 47.
    Okuno, Tsutomu
    et al.
    National Institute of Occupational Safety and Health, Japan.
    Kojima, Masami
    Dept. Of Ophthalmology, Kanazawa University.
    Schulmeister, Karl
    Sliney, David
    406 Streamside Dr, Fallston, MD 21047 USA.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Tengroth, Björn
    Opthalmoloty Karolinska Institutet, Sweden.
    Zuclich, Joseph
    Grumman IT Northrop .
    Infrared Cataract2016Report (Refereed)
  • 48.
    Sandberg Melin, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Malmberg, Filip
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Söderberg, Per G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    A strategy for OCT estimation of the optic nerve head pigment epithelium central limit-inner limit of the retina minimal distance, PIMD-2π2019In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 97, no 2, p. 208-213Article in journal (Refereed)
    Abstract [en]

    Purpose To develop a semi-automatic algorithm for estimation of pigment epithelium central limit-inner limit of the retina minimal distance averaged over 2 pi radians (PIMD-2 pi) and to estimate the precision of the algorithm. Further, the variances in estimates of PIMD-2 pi were to be estimated in a pilot sample of glaucomatous eyes. Methods Three-dimensional cubes of the optic nerve head (ONH) were captured with a commercial SD-OCT device. Raw cube data were exported for semi-automatic segmentation. The inner limit of the retina was automatically detected. Custom software aided the delineation of the ONH pigment epithelium central limit resolved in 500 evenly distributed radii. Sources of variation in PIMD estimates were analysed with an analysis of variance. Results The estimated variance for segmentations and angles was 130 mu m(2) and 1280 mu m(2), respectively. Considering averaging eight segmentations, a 95 % confidence interval for mean PIMD-2 pi was estimated to 212 +/- 10 mu m (df = 7). The coefficient of variation for segmentation was estimated at 0.05. In the glaucomatous eyes, the within-subject variance for captured volumes and for segmentations within volumes was 10 mu m(2) and 50 mu m(2), respectively. Conclusion The developed semi-automatic algorithm enables estimation of PIMD-2 pi in glaucomatous eyes with relevant precision using few segmentations of each captured volume.

  • 49.
    Sandberg Melin, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Malmberg, Filip
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Söderberg, Per G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    An OCT variable for glaucoma follow-up: Pigment epithelium central limit - Inner limit of the retina, Minimal Distance, PIMD2016In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, no 12Article in journal (Other academic)
  • 50.
    Sandberg Melin, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Nuija, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Alm, Albert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Yu, Zhaohua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Variance components in confocal scanning laser tomography measurements of neuro-retinal rim area and the effect of repeated measurements on the power to detect loss over time2016In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 94, no 7, p. 705-711Article in journal (Refereed)
    Abstract [en]

    PurposeTo estimate the variation in measurements of neuro-retinal rim area (NRA) determined by confocal scanning laser tomography and consequences for clinical follow-up. MethodsAltogether, 24 healthy subjects were randomized on -320m, Moorfields and Standard NRA plane strategies. Additionally, NRA was measured in 32 glaucoma subjects. Variance components for subjects, visits and measurements were estimated with analysis of variance. Sample sizes required to detect a 6.0x10(-2)mm(2) NRA change were estimated assuming a significance level of 0.05 and a power of 0.8. Consequences for independent group, and paired comparison design, respectively, were analysed. Further, precision in estimates within subjects over time was investigated. ResultsThe variation of NRA among subjects was considerably larger than the variation among visits and measurements. For glaucoma subjects, the variation among visits and measurements were of the same order but larger than in healthy subjects. It was found that independent group comparisons require inconveniently large sample sizes. Within-subject paired comparisons over time require sample sizes of below 15 subjects. The estimated variations for glaucoma subjects imply that 54months of follow-up is required for detection of change from baseline. ConclusionsThe variance for subjects is substantial in relation to those for visits and measurements. Cross-sectional independent group comparisons of levels of NRA are unsuitable, due to considerable subject variation. Levels of NRA differences within subjects between visits can be estimated with acceptable precision. Neuro-retinal rim area (NRA) measurement can be used for long-term follow-up of glaucoma progression.

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