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Volha Malechka, Gennadiy P Moiseyev, Yusuke Takahashi, Younghwa Shin, Jian-Xing (Jay) Ma; Impaired Retinoid Visual Cycle in Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5226. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy is a common complication of diabetes mellitus. Diabetic patients experience functional deficits in dark adaptation, contrast sensitivity and color perception before the microvascular pathologies become apparent. The mechanism that mediates these visual abnormalities remains unclear. The goal of this study was to evaluate early changes in neural retinal function and in retinoid metabolism in the eye in diabetic rats.
The rats were assigned to streptozotocin-induced diabetic and non-diabetic control groups. Blood glucose levels and body weights were monitored regularly. Retinal function was examined by electroretinography (ERG). Expression levels of rod opsin and visual cycle proteins such as RPE65, LRAT, STRA6 and IRBP were analyzed by Western blotting. The enzymatic activities of RPE65 and LRAT were assayed using HPLC. The expression level and localization of STRA6 in the retinal pigment epithelium (RPE) were confirmed by immunohistochemistry. The RBP4 level in rat serum was evaluated by ELISA. The measurement of maximal rhodopsin content was measured by absorption spectrophotometry. Retinoid profile in the eyecup and serum retinoids level were assayed using HPLC.
Diabetic animals at 4 months after onset of diabetes showed declined scotopic and photopic ERG A and B waves compared to age-matched non-diabetic control group. Western blot analysis revealed down-regulation of STRA6 and IRBP in diabetic eyes; however, it showed no significant differences in rod opsin, LRAT and RPE65 protein levels. Immunofluorescent staining of eyecup cross-sections from diabetic animals confirmed the down-regulation of STRA6 in the RPE. The maximal rhodopsin content was significantly decreased in diabetic eyes (795 ± 337 pmole/retina and 1107.5 ± 291 pmole/retina in diabetic and control group respectively; p=0.015). The 11-cis-retinal levels were significantly lower in diabetic animals than in non-diabetic control. The serum RBP4 level was significantly lower in diabetic rats (39.25 ± 8.79 pg/mL and 58.7 ± 14.5 pg/mL in diabetic and control group, respectively; p=0.01).
Rhodopsin levels are decreased and 11-cis-retinal regeneration is impaired in diabetic eyes. Most likely, disturbed rhodopsin regeneration is a result of down-regulation of STRA6, IRBP and RBP4 and consequently, the relative vitamin A deficiency in ocular tissues in diabetes.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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