Retinal degeneration is characterized by the dysfunction of retinal cells. Oxidative and endoplasmic reticulum (ER) stress play an important role in the pathogenesis and progression of retinal degeneration. Tauroursodeoxycholic acid (TUDCA) has been demonstrated to have protective effects in in vitro and in vivo retinal degeneration models. To fully understand the molecular mechanisms of TUDCA’s protection, we first treated human retinal pigment epithelial (RPE) cells, ARPE-19, with H₂O₂ or H₂O₂ plus TUDCA for 24 h. RPE cells co-exposed to TUDCA had higher cell viability and lower cell death rate compared to cells exposed to H₂O₂ alone. TUDCA significantly increased antioxidant capacity in H₂O₂-treated RPE cells by decreasing the generation of reactive oxygen species (ROS) and Malondialdehyde (MDA), upregulating the expression of antioxidant genes, and increasing the generation of glutathione (GSH). TUDCA also inhibited inflammation in H₂O₂-challenged RPE cells by decreasing the expression of proinflammatory cytokines. Furthermore, TUDCA suppressed thapsigargin-induced ER stress in RPE cells, as demonstrated by decreased the expression of CCAAT-enhancer-binding protein homologous protein (CHOP) and apoptosis. Our present study suggests that TUDCA can protect RPE cells against oxidative damage, inflammation, and ER stress and may benefit patients with retinal degeneration.

Cholesterol dysregulation has been implicated in age-related macular degeneration (AMD), the most common cause of visual impairment in the elderly. The 18 KDa translocator protein (TSPO) is a mitochondrial outer membrane protein responsible for transporting cholesterol from the mitochondrial outer membrane to the inner membrane. TSPO is highly expressed in retinal pigment epithelial (RPE) cells, and TSPO ligands have shown therapeutic potential for the treatment of AMD. Here, we characterized retinal pathology of Tspo knockout (KO) mice using histological, immunohistochemical, biochemical and molecular biological approaches. We found that Tspo KO mice had normal retinal morphology (by light microscopy) but showed elevated levels of cholesterol, triglycerides and phospholipids with perturbed cholesterol efflux in the RPE cells of Tspo KO mice. Expression of cholesterol-associated genes (Nr1h3, Abca1, Abcg1, Cyp27a1 and Cyp46a1) was significantly downregulated, and production of pro-inflammatory cytokines was markedly increased in Tspo KO retinas. Furthermore, microglial activation was also observed in Tspo KO mouse retinas. These findings provide new insights into the function of TSPO in the retina and may aid in the design of new therapeutic strategies for the treatment of AMD.