Age-related macular degeneration (AMD) is a leading cause of blindness in elderly populations, yet the molecular events that initiate the early retinal defects that lead to visual function deficits remain poorly understood. The studies here explored a role for the stress response protein Regulated in Development and DNA damage response 1 (REDD1) in the development of retinal pathology by using the oxidant stressor sodium iodate (NaIO₃) to model dry AMD in mice. REDD1 protein abundance was increased in the retinal pigmented epithelium (RPE) and retina of mice administered NaIO₃. In wild-type REDD1^+/+ mice, reactive oxygen species (ROS) levels were robustly increased in the outer retinal layers 1 day after NaIO₃ administration, with focal areas of increased ROS seen throughout the outer retina after 7 days. In contrast with REDD1^+/+ mice, ROS levels were blunted in REDD1^−/− mice after NaIO₃ administration. REDD1 was also required for upregulated expression of pro-inflammatory factors in the RPE/retina and immune cell activation in the outer retina following NaIO₃ administration. In REDD1^+/+ mice, NaIO₃ reduced RPE65 and rhodopsin levels in the RPE and photoreceptor layers, respectively. Unlike REDD1^+/+ mice, REDD1^−/− mice did not exhibit disrupted RPE integrity, retinal degeneration, or photoreceptor thinning. Overall, REDD1 deletion was sufficient to prevent retinal oxidative stress, RPE damage, immune cell activation, and photoreceptor loss in response to NaIO₃. The findings support a potential role for REDD1 in the development of retinal complications in the context of dry AMD.

年龄相关性黄斑变性 （AMD） 是老年人群失明的主要原因，但引发导致视觉功能缺陷的早期视网膜缺陷的分子事件仍然知之甚少。这里的研究通过使用氧化剂应激源碘酸钠 （NaIO₃） 来模拟小鼠的干性 AMD，探讨了应激反应蛋白 Regulated in Development 和 DNA 损伤反应 1 （REDD1） 在视网膜病理发展中的作用。REDD1 蛋白丰度在施用 NaIO₃ 的小鼠视网膜色素上皮 （RPE） 和视网膜中增加。在野生型 REDD1 ^{+ / +} 小鼠中，NaIO₃ 给药后 1 天视网膜外层的活性氧 （ROS） 水平显著增加，7 天后在整个视网膜外层看到 ROS 增加的局灶区域。与 REDD1 ^{+ / +} 小鼠相比，在 NaIO₃ 给药后，REDD1 ^{- / -} 小鼠的 ROS 水平减弱。在 NaIO₃ 给药后，RPE/视网膜中促炎因子的表达上调和视网膜外层免疫细胞激活也需要 REDD1。在 REDD1 ^{+ / +} 小鼠中，NaIO₃ 分别降低了 RPE 和光感受器层中的 RPE65 和视紫红质水平。与 REDD1 ^{+ / +} 小鼠不同，REDD1 ^{- / -} 小鼠没有表现出 RPE 完整性破坏、视网膜变性或光感受器变薄。总体而言，REDD1 缺失足以防止视网膜氧化应激、RPE 损伤、免疫细胞活化和响应 NaIO₃ 的光感受器丢失。研究结果支持 REDD1 在干性 AMD 背景下视网膜并发症发展中的潜在作用。