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  • 1.
    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.

  • 2.
    Kronschlager, Martin
    et al.
    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.
    Yu, Zhaohua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Meyer, Linda Maren
    Lofgren, Stefan
    Apoptosis in Rat Cornea After In Vivo Exposure to Ultraviolet Radiation at 300 nm2015In: Cornea, ISSN 0277-3740, E-ISSN 1536-4798, Vol. 34, no 8, p. 945-949Article in journal (Refereed)
    Abstract [en]

    Purpose:Peak toxicity for in vivo ultraviolet radiation (UVR) exposure to the lens is in the 300-nm wavelength region. However, little is known about corneal cell damage at 300 nm. The purpose of the study was to determine the time evolution of apoptosis in the cornea after in vivo exposure to 300-nm UVR.Methods:Altogether, 16 Sprague Dawley rats were divided into 4 groups and unilaterally exposed to 5 kJ/m(2) UVR ((max): 300 nm; (0.5): 10 nm) for 15 minutes. After a predetermined latency period of 1, 5, 24, and 120 hours, depending on the group, the animals were killed and eyes were enucleated. Eye globes were further cryosectioned in 10-m thick midsagittal sections. For the detection of apoptosis, the TUNEL method was applied.Results:TUNEL-positive signals were observed in the superficial epithelial cells in the exposed and control eyes at all latency periods. At 5 hours, TUNEL staining was detected in the exposed corneas in epithelial cells, keratocytes, and endothelial cells with a maximum signal at 24 hours. At 120 hours, no TUNEL staining was found in endothelial cells and only occasionally in keratocytes in exposed corneas. Signs of ulceration and stromal thinning were observed at 120 hours.Conclusions:UVR in the 300-nm wavelength region induces TUNEL staining in all 3 corneal layers. TUNEL staining of all 3 corneal layers is an early postexposure event observed after a 5-hour latency period. Corneal sterile keratolysis occurs in the time window of 24 to 120 hours probably induced by neutrophils.

  • 3.
    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.

  • 4.
    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.

  • 5.
    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.

  • 6.
    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.

  • 7.
    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.

  • 8.
    Sandberg Melin, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics. centrum för forskning och utveckling Uppsala universitet/Gävleborg.
    Yu, Zhaohua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics.
    Detection and clinical follow-up of segmental glaucomatous optic nerve head damage using OCT.Manuscript (preprint) (Other academic)
  • 9.
    Steinvall, Ove
    et al.
    Swedish Defense Research Agency.
    Sandberg, Stig
    Swedish Defense Research Agency.
    Hörberg, Ulf
    Swedish Defense Research Agency.
    Persson, Rolf
    Swedish Defense Research Agency.
    Berglund, Folke
    Swedish Defense Research Agency.
    Karlsson, Kjell
    Swedish Defense Research Agency.
    Öhgren, Johan
    Swedish Defense Research Agency.
    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.
    Laser dazzling impacts on car driver performance2013In: : Material1 ?Material x Språk: - Engelska Svenska Norska Arabiska Bokmål Bulgariska Danska Engelska Esperanto Estniska Finska Franska Färöiska Grönländska (Kalaallit oqaasi) Hebreiska Hindi Indonesiska Iriska Isländska Italienska Japanska Katalanska Kinesiska Koreanska Kroatiska Kurdiska Latin Lettiska Litauiska Madurese Makedonska Mongoliskt språk Nederländska Norska Nygrekiska (1453-) Nynorsk Odefinierat språk Persiska Polska Portugisiska Ryska Samiskt språk Sanskrit Serbiska Slovakiska Slovenska Spanska Svenska Tjeckiska Turkiska Tyska Ukrainska Ungerska Urdu Vietnamesiska, SPIE - International Society for Optical Engineering, 2013, p. 88980H-1-16Conference paper (Refereed)
    Abstract [en]

    A growing problem for the Police and Security Forces has been to prevent potentially hostile individuals to pass a checkpoint, without using lethatl violence. Therefore the question has been if there is a laser or any other strong light source that could be used as a warning and dazzling device, without lethal or long term effects. To investigate the possibilities a field trial has been performed at a motor-racing track. A green CW laser with an irradiance on the eye of maximum 0.5 MPE, as defined by ICNIRP [1] and the ANZI standard [2], was used as a dazzle source. Ten drivers have been driving with dipped headlights through a course of three lines with orange cones. In every line there has been only one gate wide enough to pass without hitting the cones. The time through the course, the choice of gates and the number of cones hit have been measured. For every second trial drive through the track, the driver was exposed to the laser dazzler. The background illuminances ranged from a thousand lux in daylight to about ten millilux in darkness. The protective effect of the sun-visor of the car was investigated. The drives visual system was carefully examined before and after experimental driving and a few weeks after the experimental driving to verify that no pathological effects, that could potentially be induced by the laser exposure, pre-existed or occurred after the laser exposure. An analysis of variance for a within subjects design has been used for evaluation. It was found that green laser light can have an obvious warning effect in daylight. Dazzling does reduce the drivers ability to make judgments and manouver the car in twilight and darkness. A sun-visor can reduce the glare and give the driver an improved control, but that perception can be unjustified. No damage to the visual system was observed.

  • 10.
    Söderberg, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Al-Saqry, Riyadh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Schulmeister, Karl
    Gallichanin, Konstantin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Kronschläger, Martin
    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.
    Photochemical effects in the lens from near infrared radiation?2009In: Proceedings of SPIE, the International Society for Optical Engineering, ISSN 0277-786X, E-ISSN 1996-756X, Vol. 7163, p. 716311-Article in journal (Refereed)
    Abstract [en]

    Conclusion: The current data are consistent with a potential photochemical effect of in vivo exposure of the crystalline lens to near infrared radiation since the onset of cataract after in just above threshold dose was at least 18 hrs delayed after the exposure. Materials and methods: The eyes of 6 weeks old Sprague-Dawley rats were exposed unilaterally in vivo to 1090 nm, 6.2 W quasi-top hat spatial distribution with a 3 mm spot on the anterior lens surface within the dilated pupil. First, four exposure time groups of rats were exposed to increasing exposure times. At 24 hrs after exposure, the difference of light scattering between the lenses from the same animal was measured. Then, based on the first experiment, four post-exposure time groups were exposed unilaterally in vivo to 8 s of 1090 nm, 6.2 W quasi-top hat spatial distribution with a 3 mm spot on the anterior lens surface within the dilated pupil. After, the intended post-exposure time, the difference of light scattering between the lenses from the same animal was measured. Results: A 3 mm spot of 6.2 W induces light scattering in the lens with exposures of at least 8 s. Further, after 8 s of 6.2 W within a 3 mm spot on the lens surface, the light scattering increase in the lens was delayed at least 18 hrs after the exposure.

  • 11.
    Söderberg, Per G.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Sandberg, Stig
    Swedish Def Res Agcy, Laser Syst Grp, Linkoping, Sweden..
    Horberg, Ulf
    Swedish Def Res Agcy, Laser Syst Grp, Linkoping, Sweden..
    Persson, Rolf
    Swedish Def Res Agcy, Laser Syst Grp, Linkoping, Sweden..
    Berglund, Folke
    Swedish Def Res Agcy, Laser Syst Grp, Linkoping, Sweden..
    Karlsson, Kjell
    Swedish Def Res Agcy, Laser Syst Grp, Linkoping, Sweden..
    Öhgren, Johan
    Swedish Def Res Agcy, Laser Syst Grp, Linkoping, Sweden..
    Yu, Zhaohua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Steinwall, Ove Steinwall Ove
    Swedish Def Res Agcy, Laser Syst Grp, Linkoping, Sweden..
    Dazzling, Laser
    Exposure to green laser decreases driving performance2015In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 56, no 7Article in journal (Refereed)
  • 12.
    Söderberg, Per G.
    et al.
    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.
    Galichanin, Konstantin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Kronschläger, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Schulmeister, Karl
    Yu, Zhaohua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Near infrared radiation damage mechanism in the lens2015In: OPHTHALMIC TECHNOLOGIES XXV / [ed] Fabrice Manns, Per G. Söderberg, Arthur Ho, 2015, Vol. 9307, article id 930717Conference paper (Refereed)
    Abstract [en]

    The current data strongly indicates that there is no photochemical effect of in vivo exposure to 1090 nm near IRR radiation within the pupil. Four groups of 20 Sprague-Dawley rats were unilaterally exposed in vivo to 96 W.cm(-2) centered inside the pupil for 10, 18, 33 and 60 min, respectively depending on group belonging. This resulted in radiant exposure doses of 57, 103, 198 and 344 kJ.cm(-2). Temperature evolution at the limbus during the exposure and difference of intensity of forward light scattering between the exposed and the contralateral not exposed eye was measured at 1 week after exposure. The temperature at the limbus was found to increase exponentially towards an asymptote with an asymptote temperature of around 7 degrees C and a time constant (1/k) of around 15 s. No increase of light scattering was found despite that the cumulated radiant exposure dose was [80; 250] times the threshold for photochemically induced cataract suggested by previous empirical data. It is concluded that at 1090 nm near IRR there is no photochemical effect.

  • 13.
    Söderberg, Per G.
    et al.
    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.
    Kronschläger, Martin
    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.
    Galichanin, Konstantin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Time evolution of light scattering in the lens and apoptosis after in vivo exposure to ultraviolet radiation2016In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, no 12Article in journal (Refereed)
  • 14.
    Söderberg, Per
    et al.
    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.
    Yu, Zhaohua
    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.
    Does infrared or ultraviolet light damage the lens?2016In: Eye (London. 1987), ISSN 0950-222X, E-ISSN 1476-5454, Vol. 30, no 2, p. 241-246Article in journal (Refereed)
    Abstract [en]

    In daylight, the human eye is exposed to long wavelength ultraviolet radiation (UVR), visible radiation and short wavelength infrared radiation (IRR). Almost all the UVR and a fraction of the IRR waveband, respectively, left over after attenuation in the cornea, is absorbed in the lens. The time delay between exposure and onset of biological response in the lens varies from immediate-to-short-to-late. After exposure to sunlight or artificial sources, generating irradiances of the same order of magnitude or slightly higher, biological damage may occur photochemically or thermally. Epidemiological studies suggest a dose-dependent association between short wavelength UVR and cortical cataract. Experimental data infer that repeated daily in vivo exposures to short wavelength UVR generate photochemically induced damage in the lens, and that short delay onset cataract after UVR exposure is photochemically induced. Epidemiology suggests that daily high-intensity short wavelength IRR exposure of workers, is associated with a higher prevalence of age-related cataract. It cannot be excluded that this effect is owing to a thermally induced higher denaturation rate. Recent experimental data rule out a photochemical effect of 1090 nm in the lens but other wavelengths in the near IRR should be investigated.

  • 15.
    Söderberg, Per
    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.
    Malmqvist, Lars D.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Sandberg-Melin, Camilla
    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.
    Talebizadeh, Nooshin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Katarakt -: ett optiskt problem i ögats lins2016In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 113, p. 1532-1536, article id D6SCArticle in journal (Refereed)
    Abstract [sv]

    Katarakt definieras som nedsatt syn på grund av en optisk störning i ögats lins.

    Cirka 50 procent av kataraktsjukdomen antas associerad med genetiska faktorer.

    Ultraviolett strålning är epidemiologiskt starkt associerad med barkkatarakt, och rökning med kärnkatarakt.

    Störning av proteinkoncentrationsgradienten i linsen orsakar ljusspridning.

    Kemiska förändringar i linsens vattenlösliga proteiner kan orsaka aggregation av dessa.

    Betydande teknisk utveckling inom kataraktkirurgi reflekteras i en linjär ökning av antalet kataraktoperationer i Sverige under de senaste 35 åren.

    I snö och vid vatten bör solglasögon av filterkategori 3 användas för att skydda ögonen.

  • 16.
    Söderberg, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics.
    Yu, Zhaohua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics.
    Sandberg Melin, Camilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Optic nerve head morphometry for glaucoma diagnosis, optimization of clinical measurement strategy2019In: Proceedings of SPIE, ISSN 0277-786X, Vol. 10858, p. 45:1-45:8, article id 108581CArticle in journal (Refereed)
    Abstract [en]

    The present study aimed to develop a strategy for evaluation of instant PIMD-2 pi measurements as a basis for clinical monitoring of glaucoma. PIMD-2 pi is a morphometric measure of the waist of the nerve fiber layer at the optic nerve head (ONH). Clinical measurements of PIMD-2 pi in patients with early to moderate stage glaucoma demonstrated a high variability among subjects. The high variability among subjects renders comparison of instant PIMD-2 pi measurements to tolerance limits for normality derived from a normative database inefficient. It is suggested to instead compare sequential measurements of PIMD-2 pi within a patient. Initially, the difference between an instant measurement and the average of previous measurements can be compared to tolerance limits for difference between measurements within subject. Once, a potential loss of PIMD-2 pi is detected, a sufficient number of measurements within a sufficiently wide time interval can be used to estimate the PIMD-2 pi loss rate with regression and the deviation of the estimated loss rate can be evaluated as a 95 % confidence interval for the loss rate. If the upper confidence limit excludes 0, a significant loss rate has been detected. The currently proposed strategy has the potential to detect glaucoma earlier than the current gold standard, computer perimetry, with less inconvenience for the patient.

  • 17.
    Talebizadeh, Nooshin
    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.
    Kronschläger, Martin
    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.
    Modelling the time evolution of active caspase-3 protein in the rat lens after in vivo exposure to Ultraviolet radiation-B: Model for active caspase-3 expression after in vivo exposure to UVR-300 nm2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 9, p. e106926-Article in journal (Refereed)
    Abstract [en]

    Purpose: To introduce a model for the time evolution of active caspase-3 protein expression in albino rat lens up to 24 hours after in vivo exposure to low dose UVR in the 300 nm wavelength region (UVR-300 nm).

    Methods: Forty Sprague-Dawley rats were unilaterally exposed in vivo to 1 kJ/m2 UVR-300 nm for 15 minutes. At 0.5, 8, 16, and 24 hours after the UVR exposure, the exposed and contralateral not-exposed lenses were removed and processed for immunohistochemistry. The differences in the probability of active caspase-3 expression at four different time points after exposure were used to determine the time evolution of active caspase-3 expression. A logistic model was introduced for the expression of active caspase-3. The parameters for the exposed and the not exposed lenses were estimated for the observation time points.

    Results: The exposure to UVR-300 nm impacted on the parameters of the logistic model. Further, the parameters of the model varied with time after exposure to UVR-300 nm.

    Conclusion: The logistic model predicts the impact of exposure to UVR-300 nm on the spatial distribution of probability of active caspase-3 protein expression, depending on time.

  • 18.
    Talebizadeh, Nooshin
    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.
    Kronschläger, Martin
    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.
    Time evolution of active caspase-3 labelling after in vivo exposure to UVR-300 nm2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 8, p. 769-773Article in journal (Refereed)
    Abstract [en]

    PURPOSE:To determine the time evolution of active caspase-3 protein expression in albino rat lens after in vivo exposure to low-dose UVR-300 nm, as detected by immunofluorescence.

    METHODS:Forty Sprague-Dawley rats were unilaterally exposed in vivo to 1 kJ/m2 UVR-300 nm for 15 min. At 0.5, 8, 16 and 24 hr after the UVR exposure, the exposed and contralateral nonexposed lenses were removed and processed for immunohistochemistry. Three mid-sagittal sections from each lens were stained. The cells labelled for active caspase-3 in each section of both the exposed and nonexposed lenses were counted and recorded three times. The difference of the proportion of labelling between the exposed and contralateral nonexposed lenses within each animal was calculated. The differences of active caspase-3 labelling at four different time-points after exposure were used to determine the time evolution of active caspase-3 expression.

    RESULTS:Caspase-3 expression was higher in the exposed than in contralateral nonexposed lenses. The mean difference between the exposed and contralateral nonexposed lenses, including all lenses from all time intervals, was 0.12 ± 0.01 (= CI 95%). The mean differences between the exposed and contralateral nonexposed lenses were 0.11 ± 0.02, 0.13 ± 0.02, 0.14 ± 0.01 and 0.09 ± 0.03 (= CI 95%) for the 0.5-, 8-, 16- and 24-hr time groups, respectively. The orthogonal comparison showed no difference in the expression of active caspase-3 between the 0.5- and the 24-hr groups (Test statistic 1.50, F1,36 = 4.11, p < 0.05) or between the 8- and the 16-hr groups (test statistic 0.05, F1,36 = 4.11, p < 0.05). There was a difference when comparing the 0.5- and 24-hr groups to the 8- and 16-hr groups (test statistic 7.01, F1,36 = 4.11, p < 0.05).

    CONCLUSION:The expression of active caspase-3 in the lens epithelium increases after UVR exposure. There is a peak of expression approximately 16 hr after the exposure.

  • 19.
    Talebizadeh, Nooshin
    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.
    Martin, Kronschläger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Finn, Hallböök
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience.
    Per, Söderberg
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Specific spatial distribution of caspase-3 in normal lenses2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 93, no 3, p. 289-292Article in journal (Refereed)
    Abstract [en]

    Purpose

    To determine the distribution of active caspase-3 in rat eye lens epithelium.

    Methods

    In total, 120 sagittal sections from forty rats were assessed for active caspase-3 labelling using immunohistochemistry. Lens epithelial cells were counted, and the fraction of active caspase-3 labelled cells and their relative positions were identified in each section.

    Results

    Active caspase-3 is present in normal lens epithelium. The active caspase-3 expression was higher in the anterior pole of the lens. Probability of radial spatial distribution of labelling was fitted with a logistic model. The increase rate and the inflection point were estimated as CI (0.95) to 23 ± 3 cells and 114 ± 3 cells, respectively.

    Conclusion

    The gradually decreasing active caspase-3 labelling from the anterior pole to the periphery suggests that active caspase-3 may be involved in normal protein turnover caused by, for example, incident light.

  • 20.
    Talebizadeh, Nooshin
    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.
    Zhou Hagström, Nanna
    Wählby, Carolina
    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.
    Automatic quantification of fluorescence signal in rat lens epithelium2016In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, no 12, article id 3066Article in journal (Refereed)
  • 21.
    Talebizadeh, Nooshin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Zhou Hagström, Nanna
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction.
    Yu, Zhaohua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Kronschläger, Martin
    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.
    Wählby, Carolina
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction.
    Objective automated quantification of fluorescence signal in histological sections of rat lensManuscript (preprint) (Other academic)
    Abstract [en]

    Purpose: To develop an automated method to delineate lens epithelial cells and to quantify expression of fluorescent signal of biomarkers in each nucleus and cytoplasm of lens epithelial cells in a histological section.

    Methods: An automated algorithm was developed in Matlab™ to localize and quantify fluorescence signal in lens epithelial cells in histological images. A region of interest representing the lens epithelium was manually demarcated in each input image. Individual cell nuclei within the region of interest were automatically delineated based on watershed segmentation and thresholding. Fluorescence signal was quantified within nuclei and cytoplasms. The classification of fluorescence signal was based on local background. Classification of cells as labelled or not labelled was thereafter optimized as compared to visual classification of a limited dataset.

    The performance of the automated classification was evaluated by asking eleven independent blinded observers to classify all cells (n=395) in one lens image. Time consumed by the automatic algorithm and visual /manual classification of nuclei, was recorded.

    Results: On an average, 77 % of the cells were correctly classified as compared to the majority vote of the visual observers. The average agreement among visual observers was 83 %. However, variation among visual observers was high, and agreement between two visual observers was as low as 71 % in the worst case. Automated classification was on average 10 times faster than manual scoring.

    Conclusion: The presented method enables objective and fast detection of lens epithelial cells and quantification of expression of fluorescent signal in a histological section of rat lens, with accuracy comparable to the variability between different visual observers. Furthermore, automated scoring is unbiased and reproducible, and results in a 10-fold increase in throughput.

  • 22.
    Talebizadeh, Nooshin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Zhou Hagström, Nanna
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Yu, Zhaohua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Kronschläger, Martin
    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.
    Wählby, Carolina
    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. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Objective automated quantification of fluorescence signal in histological sections of rat lens2017In: Cytometry Part A, ISSN 1552-4922, E-ISSN 1552-4930, Vol. 91, no 8, p. 815-821Article in journal (Refereed)
    Abstract [en]

    Visual quantification and classification of fluorescent signals is the gold standard in microscopy. The purpose of this study was to develop an automated method to delineate cells and to quantify expression of fluorescent signal of biomarkers in each nucleus and cytoplasm of lens epithelial cells in a histological section. A region of interest representing the lens epithelium was manually demarcated in each input image. Thereafter, individual cell nuclei within the region of interest were automatically delineated based on watershed segmentation and thresholding with an algorithm developed in Matlab™. Fluorescence signal was quantified within nuclei, cytoplasms and juxtaposed backgrounds. The classification of cells as labelled or not labelled was based on comparison of the fluorescence signal within cells with local background. The classification rule was thereafter optimized as compared with visual classification of a limited dataset. The performance of the automated classification was evaluated by asking 11 independent blinded observers to classify all cells (n = 395) in one lens image. Time consumed by the automatic algorithm and visual classification of cells was recorded. On an average, 77% of the cells were correctly classified as compared with the majority vote of the visual observers. The average agreement among visual observers was 83%. However, variation among visual observers was high, and agreement between two visual observers was as low as 71% in the worst case. Automated classification was on average 10 times faster than visual scoring. The presented method enables objective and fast detection of lens epithelial cells and quantification of expression of fluorescent signal with an accuracy comparable with the variability among visual observers.

  • 23.
    Yu, Zhaohua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Damage mechanisms for near-infrared radiation induced cataract2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Purpose: 1) To estimate the threshold dose and the time evolution for cataract induction by near infrared radiation (IRR) in seconds exposure time domain; 2) to determine the ocular temperature development during the threshold exposure; 3) to investigate if near IRR induces cumulative lens damage considering irradiance exposure time reciprocity; 4) to experimentally estimate the temperature in the lens indirectly from the measurement of temperature-induced light scattering increase.

    Methods: Before exposure, 6-weeks-old albino rats were anesthetized and the pupils of both eyes were dilated. Then the animals were unilaterally exposed to 1090 nm IRR within the pupil area. Temperature was recorded with thermocouples placed in the selected positions of the eye. At the planned post-exposure time, the animal was sacrificed and the lenses were extracted for measurements of forward light scattering and macroscopic imaging (Paper I-III). In Paper IV, the lens was extracted from six-weeks-old albino Sprague-Dawley female rats and put into a temperature-controlled cuvette filled with balanced salt solution. Altogether, 80 lenses were equally divided on four temperature groups, 37, 40, 43 and 46 ºC. Each lens was exposed for 5 minutes to temperature depending on group belonging while the intensity of forward light scattering was recorded.

    Results: The in vivo exposure to 197 W/cm2 1090 nm IRR required a minimum 8 s for cataract induction. There was approximately 16 h delay between exposure and light scattering development in the lens. The same radiant exposure was found to cause a temperature increase of 10 °C at the limbus and 26 °C close to the retina. The in vivo exposure to 96 W/cm2 1090 nm IRR with exposure time up to 1 h resulted in an average temperature elevation of 7 °C at the limbus with the cornea humidified and no significant light scattering was induced one week after exposure. Arrhenius equation implies that the natural logarithm of the inclination coefficient for light scattering increase is linearly dependent on the inverse of the temperature. The proportionality constant and the intercept, estimated as CI(0.95)s, were 9.6±2.4 x103 K and 22.8±7.7. Further, it implies that if averaging 20 measurements of inclination coefficients in a new experiment at constant heat load, the confidence limits for prediction of temperature correspond to ±1.9 °C.

    Conclusions: It is indicated that IRR at 1090 nm produces thermal but not cumulatively photochemical cataract, probably by indirect heat conduction from absorption in tissues surrounding the lens. Applying the Arrhenius equation the in vivo temperature in the lens can be determined retrospectively with sufficient resolution.

    List of papers
    1. 1090 nm infrared radiation at close to threshold dose induces cataract with a time delay
    Open this publication in new window or tab >>1090 nm infrared radiation at close to threshold dose induces cataract with a time delay
    Show others...
    2015 (English)In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 93, no 2, p. e118-e122Article in journal (Refereed) Published
    Abstract [en]

    Purpose

    To investigate if infrared radiation induced cataract is instant or is associatedwith a time delay between the exposure and the onset of lens light scattering after anexposure to just above threshold dose.

    Methods

    Six-weeks-old albino Sprague-Dawley female rats were unilaterally exposedto 197 W/cm2 infrared radiation at 1090 nm within the dilated pupil. In the firstexperiment, the animals were exposed with four exposure times of 5, 8, 13 and 20 s,respectively. At 24 h after exposure, the light scattering in both exposed andcontralateral not exposed lenses was measured. Based on the first experiment, fourpost exposure time groups were exposed unilaterally to 1090 nm infrared radiation of197 W/cm2 for 8 s. At 6, 18, 55 and 168 h after exposure, the light scattering in bothlenses was measured.

    Results

    A 197 W/cm2 infrared radiation induced light scattering in the lens withexposures of at least 8 s. Further, after exposure to infrared radiation of 197 W/cm2for 8 s, the light scattering increase in the lens was delayed approximately 16 h afterthe exposure.

    Conclusion

    There is a time delay between the exposure and the onset of cataract afterexposure to close to threshold dose implicating that either near infrared radiationcataract is photochemical or there is a time delay in the biological expression ofthermally induced damage.

    Keywords
    infrared radiation, forward light scattering, lens, photochemical, thermal
    National Category
    Basic Medicine Ophthalmology
    Research subject
    Ophtalmology
    Identifiers
    urn:nbn:se:uu:diva-226530 (URN)10.1111/aos.12508 (DOI)000349900200005 ()
    Available from: 2014-06-18 Created: 2014-06-18 Last updated: 2018-01-11Bibliographically approved
    2. Temperature-controlled in vivo ocular exposure to 1090-nm radiation suggests that near-infrared radiation cataract is thermally induced
    Open this publication in new window or tab >>Temperature-controlled in vivo ocular exposure to 1090-nm radiation suggests that near-infrared radiation cataract is thermally induced
    Show others...
    2015 (English)In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 20, no 1, article id 015003Article in journal (Refereed) Published
    Abstract [en]

    The damage mechanism for near infrared radiation induced (IRR) cataract is unclear. Both a photochemical and a thermal mechanism were suggested.

    The current paper aims to elucidate a photochemical effect based on investigation of irradiance-exposure time reciprocity.

    Groups of 20 rats were unilaterally exposed to 96 W/cm2 IRR at 1090 nm within the dilated pupil accumulating 57, 103, 198, 344 kJ/cm2 respectively. Temperature was recorded at the limbus of the exposed eye. Seven days after exposure, the lenses were macroscopically imaged and light scattering was measured quantitatively.

    The average maximum temperature increase for exposure time 10, 18, 33, 60 minutes was expressed as CI(0.95); 7.0±1.1, 6.8±1.1, 7.6±1.3, 7.4±1.1 ºC at the limbus of the exposed eye. The difference of light scattering in the lenses between exposed and contralateral not exposed eyes was 0.00±0.02, 0.01±0.03, -0.01±0.02, -0.01±0.03 tEDC, respectively and no apparent morphological changes in the lens were observed.

    An exposure to 96 W/cm2 1090 nm IRR projected on the cornea within the dilated pupil accumulating radiant exposures up to 344 kJ/cm2 does not induce cataract if the temperature rise at the limbus is below 8 °C. This is consistent with a thermal damage mechanism for IRR induced cataract.

    Keywords
    infrared radiation, temperature, forward light scattering, lens
    National Category
    Ophthalmology
    Identifiers
    urn:nbn:se:uu:diva-240718 (URN)10.1117/1.JBO.20.1.015003 (DOI)000350206400007 ()25602780 (PubMedID)
    Available from: 2015-01-08 Created: 2015-01-08 Last updated: 2017-12-05Bibliographically approved
    3. Ocular temperature elevation induced by threshold in vivo exposure to 1090 nm infrared radiation and associated heat diffusion
    Open this publication in new window or tab >>Ocular temperature elevation induced by threshold in vivo exposure to 1090 nm infrared radiation and associated heat diffusion
    Show others...
    2014 (English)In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 19, no 10, p. 105008-Article in journal (Refereed) Published
    Abstract [en]

    An in vivo exposure to 197 W/cm2 1090 nm infrared radiation (IRR) requires a minimum 8 s for cataract induction. The present study aims to determine the ocular temperature evolution and the associated heat flow at the same exposure conditions. Two groups of 12 rats were unilaterally exposed within the dilated pupil with a close to collimated beam between lens and retina. Temperature was recorded with thermocouples. Within 5 min after exposure, the lens light scattering was measured. In one group, the temperature rise in the exposed eye, expressed as CI(0.95), was 11±3 ºC at the limbus, 16±6 ºC in the vitreous behind lens and 16±7 ºC on the sclera next to the optic nerve, respectively. In the other group, the temperature rise in the exposed eye was 9±1 ºC at the limbus and 26±11 ºC on the sclera next to the optic nerve, respectively. The difference of forward light scattering between exposed and contralateral not exposed eye was 0.01±0.09 tEDC. An exposure to 197 W/cm2 1090 nm IRR for 8 s induces a temperature increase of 10 °C at the limbus and 26 °C close to the retina. IRR cataract is probably of thermal origin.

    Keywords
    infrared radiation, temperature, light scattering lens, heat diffusion
    National Category
    Neurosciences
    Research subject
    Ophtalmology
    Identifiers
    urn:nbn:se:uu:diva-232619 (URN)10.1117/1.JBO.19.10.105008 (DOI)000345837200015 ()
    Available from: 2014-09-22 Created: 2014-09-22 Last updated: 2018-05-16Bibliographically approved
    4. Measuring temperature in the lens during experimental heat load indirectly as light scattering increase rate
    Open this publication in new window or tab >>Measuring temperature in the lens during experimental heat load indirectly as light scattering increase rate
    2017 (English)In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 22, no 1, article id 015005Article in journal (Refereed) Published
    Abstract [en]

    The current study aims to experimentally estimate the temperature in the lens due to heat load indirectly from the measurement of increase rate of temperature-induced light scattering. The lens was extracted from Sprague-Dawley rats and put into a temperature-controlled cuvette filled with balanced salt solution. Altogether, 80 lenses were equally divided on four temperature groups. Each lens was exposed for 5 minutes to temperature depending on group belonging while the intensity of forward light scattering was recorded. The inclination coefficient of light scattering increase at the temperature 37, 40, 43, and 46 ºC was estimated as a CI(0.95), 3.1±0.8, 4.4±0.8, 5.5±0.9 and 7.0±0.8 x10-4 tEDC/s, respectively. The Arrhenius equation implies that the natural logarithm of the inclination coefficient is linearly dependent on the inverse of the temperature. The proportionality constant and the intercept were 9.6±2.4 x103 K and 22.8±7.7. The activation energy was 8.0±2.0 x101 kJ·mol-1. The current experiment implies that if averaging 20 measurements of inclination coefficients in a new experiment at constant heat load, the confidence limits for predicted temperature correspond to ±1.9 °C. With the proportionality constant and the intercept estimated in the current experiment, the in vivo temperature in the lens can be determined retrospectively with sufficient resolution.

    Keywords
    forward light scattering; lens; cataract; temperature; Arrhenius equation
    National Category
    Neurosciences
    Research subject
    Ophtalmology
    Identifiers
    urn:nbn:se:uu:diva-308820 (URN)10.1117/1.JBO.22.1.015005 (DOI)000396370600009 ()
    Available from: 2016-11-30 Created: 2016-11-30 Last updated: 2018-01-13Bibliographically approved
  • 24.
    Yu, Zhaohua
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Persson, Rolf
    Swedish Defence Research Agency.
    Öhgren, Johan
    Swedish Defence Research Agency.
    Sandberg, Stig
    Swedish Defence Research Agency.
    Hörberg, Ulf
    Swedish Defence Research Agency.
    Berglund, Folke
    Swedish Defence Research Agency.
    Karlsson, Kjell
    Swedish Defence Research Agency.
    Steinvall, Ove
    Swedish Defence Research Agency.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Green light laser exposure at 532nm near the exposure limit during a human volunteer vehicle driving task does not alter structure or function in the visual system2014In: Journal of laser applications, ISSN 1042-346X, E-ISSN 1938-1387, Vol. 26, no 2, p. 022009-1-022009-7Article in journal (Refereed)
    Abstract [en]

    This study aimed to verify nonexistence of clinically important pathological effects to the visual system after exposure to 532 nm green laser light close to the exposure limit. The present medical surveillance of vision and visual health reported in this paper is the conjunction with a study of driver performance in the presence of 532 nm laser induced glare. The driving time varied between 25 and 55 s, depending on background luminance. The laser was on during the complete test drive. The peak corneal irradiance typically was 3.5Wm2 in one test drive. Considering a typical test drive, the typical time integrated corneal radiant exposure for one test drive was estimated to be 53 J/m2. The number of test drives varied among drivers but was typically 50, thus resulting in a cumulative corneal exposure dose of approximately 2.7 kJ/m2. Altogether, ten subjects were recruited according to inclusion and exclusion criteria. All ten subjects were examined for visual acuity, intraocular pressure, contrast sensitivity, color vision, monocular reading speed, and eye structure with clinical slit-lamp microscopy examination and indirect retinoscopy. All subjects were examined before exposure, immediately after exposure, and finally within an interval between 1 week and 4 weeks after exposure. There was no significant change of visual acuity, intraocular pressure, contrast sensitivity, color vision, or monocular reading speed between before and after exposure. No abnormal ocular structure was detected after exposure. This study demonstrates that close to exposure limit, exposure to 532 nm green laser light during a vehicle driving task does not induce structural or functional damage to the human visual system as observed in the interval minutes to weeks after exposure.

  • 25.
    Yu, Zhaohua
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Schulmeister, Karl
    Talebizadeh, Nooshin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Kronschläger, Martin
    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.
    Ocular temperature elevation induced by threshold in vivo exposure to 1090 nm infrared radiation and associated heat diffusion2014In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 19, no 10, p. 105008-Article in journal (Refereed)
    Abstract [en]

    An in vivo exposure to 197 W/cm2 1090 nm infrared radiation (IRR) requires a minimum 8 s for cataract induction. The present study aims to determine the ocular temperature evolution and the associated heat flow at the same exposure conditions. Two groups of 12 rats were unilaterally exposed within the dilated pupil with a close to collimated beam between lens and retina. Temperature was recorded with thermocouples. Within 5 min after exposure, the lens light scattering was measured. In one group, the temperature rise in the exposed eye, expressed as CI(0.95), was 11±3 ºC at the limbus, 16±6 ºC in the vitreous behind lens and 16±7 ºC on the sclera next to the optic nerve, respectively. In the other group, the temperature rise in the exposed eye was 9±1 ºC at the limbus and 26±11 ºC on the sclera next to the optic nerve, respectively. The difference of forward light scattering between exposed and contralateral not exposed eye was 0.01±0.09 tEDC. An exposure to 197 W/cm2 1090 nm IRR for 8 s induces a temperature increase of 10 °C at the limbus and 26 °C close to the retina. IRR cataract is probably of thermal origin.

  • 26.
    Yu, Zhaohua
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Schulmeister, Karl
    Talebizadeh, Nooshin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Kronschläger, Martin
    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.
    Temperature-controlled in vivo ocular exposure to 1090-nm radiation suggests that near-infrared radiation cataract is thermally induced2015In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 20, no 1, article id 015003Article in journal (Refereed)
    Abstract [en]

    The damage mechanism for near infrared radiation induced (IRR) cataract is unclear. Both a photochemical and a thermal mechanism were suggested.

    The current paper aims to elucidate a photochemical effect based on investigation of irradiance-exposure time reciprocity.

    Groups of 20 rats were unilaterally exposed to 96 W/cm2 IRR at 1090 nm within the dilated pupil accumulating 57, 103, 198, 344 kJ/cm2 respectively. Temperature was recorded at the limbus of the exposed eye. Seven days after exposure, the lenses were macroscopically imaged and light scattering was measured quantitatively.

    The average maximum temperature increase for exposure time 10, 18, 33, 60 minutes was expressed as CI(0.95); 7.0±1.1, 6.8±1.1, 7.6±1.3, 7.4±1.1 ºC at the limbus of the exposed eye. The difference of light scattering in the lenses between exposed and contralateral not exposed eyes was 0.00±0.02, 0.01±0.03, -0.01±0.02, -0.01±0.03 tEDC, respectively and no apparent morphological changes in the lens were observed.

    An exposure to 96 W/cm2 1090 nm IRR projected on the cornea within the dilated pupil accumulating radiant exposures up to 344 kJ/cm2 does not induce cataract if the temperature rise at the limbus is below 8 °C. This is consistent with a thermal damage mechanism for IRR induced cataract.

  • 27.
    Yu, Zhaohua
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Schulmeister, Karl
    Talebizadeh, Nooshin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Kronschläger, Martin
    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.
    1090 nm infrared radiation at close to threshold dose induces cataract with a time delay2015In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 93, no 2, p. e118-e122Article in journal (Refereed)
    Abstract [en]

    Purpose

    To investigate if infrared radiation induced cataract is instant or is associatedwith a time delay between the exposure and the onset of lens light scattering after anexposure to just above threshold dose.

    Methods

    Six-weeks-old albino Sprague-Dawley female rats were unilaterally exposedto 197 W/cm2 infrared radiation at 1090 nm within the dilated pupil. In the firstexperiment, the animals were exposed with four exposure times of 5, 8, 13 and 20 s,respectively. At 24 h after exposure, the light scattering in both exposed andcontralateral not exposed lenses was measured. Based on the first experiment, fourpost exposure time groups were exposed unilaterally to 1090 nm infrared radiation of197 W/cm2 for 8 s. At 6, 18, 55 and 168 h after exposure, the light scattering in bothlenses was measured.

    Results

    A 197 W/cm2 infrared radiation induced light scattering in the lens withexposures of at least 8 s. Further, after exposure to infrared radiation of 197 W/cm2for 8 s, the light scattering increase in the lens was delayed approximately 16 h afterthe exposure.

    Conclusion

    There is a time delay between the exposure and the onset of cataract afterexposure to close to threshold dose implicating that either near infrared radiationcataract is photochemical or there is a time delay in the biological expression ofthermally induced damage.

  • 28.
    Yu, Zhaohua
    et al.
    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.
    Kronschläger, Martin
    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.
    Measuring temperature in the lens during experimental heat load indirectly as light scattering increase rate2017In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 22, no 1, article id 015005Article in journal (Refereed)
    Abstract [en]

    The current study aims to experimentally estimate the temperature in the lens due to heat load indirectly from the measurement of increase rate of temperature-induced light scattering. The lens was extracted from Sprague-Dawley rats and put into a temperature-controlled cuvette filled with balanced salt solution. Altogether, 80 lenses were equally divided on four temperature groups. Each lens was exposed for 5 minutes to temperature depending on group belonging while the intensity of forward light scattering was recorded. The inclination coefficient of light scattering increase at the temperature 37, 40, 43, and 46 ºC was estimated as a CI(0.95), 3.1±0.8, 4.4±0.8, 5.5±0.9 and 7.0±0.8 x10-4 tEDC/s, respectively. The Arrhenius equation implies that the natural logarithm of the inclination coefficient is linearly dependent on the inverse of the temperature. The proportionality constant and the intercept were 9.6±2.4 x103 K and 22.8±7.7. The activation energy was 8.0±2.0 x101 kJ·mol-1. The current experiment implies that if averaging 20 measurements of inclination coefficients in a new experiment at constant heat load, the confidence limits for predicted temperature correspond to ±1.9 °C. With the proportionality constant and the intercept estimated in the current experiment, the in vivo temperature in the lens can be determined retrospectively with sufficient resolution.

  • 29.
    Yu, Zhaohua
    et al.
    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.
    Kronschläger, Martin
    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.
    Indirect temperature measurement in the lens with temperature induced light scattering2016In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, no 12Article in journal (Refereed)
1 - 29 of 29
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