Transcriptome comparison between Old vs young rat retinae

Visual decline in the elderly is often attributable to retinal aging, which predisposes the tissue to pathologies including age-related macular degeneration. Currently, effective oral pharmacological interventions for retinal degeneration are limited. Utilizing the Fischer 344 rat model of aging, we evaluated the efficacy of 8-aminoguanine (8-AG), a compound previously shown for multi-organ protection, against age-related retinal degeneration. Remarkably, administration of 8-AG at a dosage of 5 mg/kg body weight via drinking water from 22 months of age for a duration of 8 weeks resulted in substantial retinal preservation evidenced by an increase in retinal thickness, a greater number of photoreceptors with longer outer segments, and enhanced electroretinogram signals. RNA sequencing and subsequent analyses revealed pronounced anti-inflammatory effects by 8-AG on both adaptive and innate immune responses within the aged retina.老年人视力衰退常归因于视网膜衰老，后者会使视网膜组织易罹患包括年龄相关性黄斑变性(age-related macular degeneration)在内的多种眼部病理病症。目前，针对视网膜变性的有效口服药物干预手段仍十分有限。本研究采用衰老型Fischer 344大鼠模型，评估了此前被证实具有多器官保护作用的化合物8-氨基鸟嘌呤(8-aminoguanine, 8-AG)对抗年龄相关性视网膜变性的功效。值得注意的是，从大鼠22月龄开始，通过饮水以5mg/kg体重的剂量给予8-AG，持续给药8周后，可实现显著的视网膜保护效果：具体表现为视网膜厚度增加、感光细胞外节更长且数量更多，以及视网膜电图(electroretinogram)信号增强。RNA测序(RNA sequencing)及后续分析显示，8-AG可对衰老视网膜内的适应性免疫与固有免疫反应产生显著的抗炎作用。