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Protective Effect of The Thioltransferase Gene On In Vivo UVR-300 nm Induced Cataract: In vivo protection of Grx1 against UVR in the lens
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology. (Per Söderberg)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology. (Per Söderberg)
Dept. of Statistics, UCLA. (Joakim Ekström)
(Marjorie Lou)
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2012 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, Vol. 53, no 1, 248-252 p.Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
2012. Vol. 53, no 1, 248-252 p.
National Category
Medical and Health Sciences
Research subject
URN: urn:nbn:se:uu:diva-163795DOI: 10.1167/iovs.11-8504ISI: 000302694500039OAI: oai:DiVA.org:uu-163795DiVA: diva2:464890
Available from: 2011-12-14 Created: 2011-12-14 Last updated: 2015-01-23Bibliographically 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.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1036
cataract, ultraviolet radiation, apoptosis, thioltransferase, caffeine
National Category
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)
Available from: 2014-11-06 Created: 2014-09-28 Last updated: 2015-01-23

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