Diabetic retinopathy is one of the most frequent causes of blindness in adults in the Western countries. Although diabetic retinopathy is considered a vascular disease, several reports demonstrate that retinal neurons are also affected, leading to vision loss. Tauroursodeoxycholic acid (TUDCA), an endogenous bile acid, has proven to be neuroprotective in several models of neurodegenerative diseases, including models of retinal degeneration. Since hyperglycemia is considered to play a central role in retinal cell dysfunction and degeneration, underlying the progression of diabetic retinopathy, the purpose of this study was to investigate the neuroprotective effects of TUDCA in rat retinal neurons exposed to elevated glucose concentration. We found that TUDCA markedly decreased cell death in cultured retinal neural cells induced by exposure to elevated glucose concentration. In addition, TUDCA partially prevented the release of apoptosis-inducing factor (AIF) from the mitochondria, as well as the subsequent accumulation of AIF in the nucleus. Biomarkers of oxidative stress, such as protein carbonyl groups and reactive oxygen species production, were markedly decreased after TUDCA treatment as compared to cells exposed to elevated glucose concentration alone. In conclusion, TUDCA protected retinal neural cell cultures from cell death induced by elevated glucose concentration, decreasing mito-nuclear translocation of AIF. The antioxidant properties of TUDCA might explain its cytoprotection. These findings may have relevance in the treatment of diabetic retinopathy patients.
Keywords: 2,4-dinitrophenylhydrazine; 2′,7′-dichlorodihydrofluorescein diacetate; AGEs; AIF; BBS; Bardet–Biedl syndrome; DCF; DNPH; DPBS; Dulbecco’s PBS solution; ECF; EDTA; EGTA; FITC; H(2)DCF-DA; PS; ROS; SDS; TUDCA; TUNEL; UDCA; advanced glycation end products; apoptosis-inducing factor; diabetes; diabetic retinopathy; dichlorodihydrofluorescein; enhanced chemifluorescence; ethylene glycol tetraacetic acid; ethylenediaminetetraacetic acid; fluorescein isothiocyanate; neural apoptosis; phosphatidylserine; reactive oxygen species; retina; sodium dodecyl sulfate; tauroursodeoxycholic acid; terminal transferase dUTP nick end labeling; ursodeoxycholic acid.
Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.