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Caffeine eye drops protect against UV-B cataract
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
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2013 (English)In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 113, 26-31 p.Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
2013. Vol. 113, 26-31 p.
Keyword [en]
caffeine, cataract, ultraviolet radiation, protection factor
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-208371DOI: 10.1016/j.exer.2013.04.015ISI: 000322931700004OAI: oai:DiVA.org:uu-208371DiVA: diva2:652327
Available from: 2013-09-30 Created: 2013-09-30 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Prevention of Experimental Cataract Induced by UVR
Open this publication in new window or tab >>Prevention of Experimental Cataract Induced by UVR
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cataract is the leading cause of blindness in the world and is defined by opacification of the normally transparent lens of the eye. The major avoidable cause of cataract is ultraviolet radiation (UVR), but no current strategies have been developed to prevent the onset of cataract. Apoptosis and internal and external antioxidant systems that inhibit apoptosis have been shown to play a significant role in cataractogenesis.

The main purposes of this thesis were to study the time evolution of apoptosis, to develop the concept of a protection factor (PF), and to investigate the effect of thioltransferase (Grx1) and topical caffeine in UVR cataract development. Further, to elucidate pharmacokinetics and influence on iris diameter of topical caffeine.

Sprague Dawley rats were exposed to UVR and TUNEL staining of the lens sections was analysed. Grx1+/+ and Grx1-/- mice were exposed to 5 sub-doses of UVR. Based on the difference of light scattering between Grx1+/+ and Grx1-/- mice, the concept of the PF was developed. Topical caffeine and a placebo were applied to the eyes of separate groups of Sprague Dawley rats that were exposed to sub-doses of UVR and protective effect was evaluated. Penetration of topical caffeine in Sprague Dawley rats to lens and blood was analysed by high performance liquid chromatography. Pupil diameter was measured in groups of unilaterally and bilaterally caffeine-treated ketamine/xylazine anesthetized Sprague Dawley rats.

TUNEL-labeling peaked between 5 and 120 hours after UVR exposure. The PF of Grx1 was 1.3. Moreover, topically administered caffeine protected against UVR-induced cataract development with a PF of 1.23. Topical caffeine peaked at 30 min in the lens, increased up to 120 min in the blood and antagonized ketamine/xylazine-induced mydriasis.

In conclusion, UVR induces apoptosis, which is evidenced by the peak of TUNEL-labeling at 24 hours after UVR exposure. The PF is an objective relative measure of protective properties that allows the comparison of different antioxidant systems and administered antioxidant substances. Grx1 and caffeine are protective against UVR-induced cataract. Topically administered caffeine penetrates to the lens and inhibits UVR-induced apoptosis. Additionally, a miotic effect of caffeine is described for the first time.

Place, publisher, year, edition, pages
Uppsala: Uppsala universitet, 2014. 44 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1036
Keyword
cataract, ultraviolet radiation, apoptosis, thioltransferase, caffeine
National Category
Ophthalmology
Identifiers
urn:nbn:se:uu:diva-232955 (URN)978-91-554-9055-3 (ISBN)
Public defence
2014-11-28, Enghoffsalen, Ing. 50, plan 1., Akademiska Sjukhuset, Uppsala, 13:00 (English)
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Supervisors
Available from: 2014-11-06 Created: 2014-09-28 Last updated: 2015-01-23

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Kronschläger, MartinYu, ZhaohuaTalebizadeh, NooshinSöderberg, Per

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