Department of Biological and Biomedical Sciences, Glasgow Caledonian University, UK.
Department of Biological and Biomedical Sciences, Glasgow Caledonian University, UK; Department of Biology, Faculty of Science, University of Zakho, Kurdistan Region, Iraq.
Exp Eye Res. 2021 Jul;208:108625. doi: 10.1016/j.exer.2021.108625. Epub 2021 May 20.
Age-related Macular Degeneration (AMD) is a major cause of sight impairment in the elderly with complex aetiology involving genetics and environment and with limited therapeutic options which have limited efficacy. We have previously shown in a mouse-model of the condition, induced by feeding a high fat diet, that adverse effects of the diet can be reversed by co-administration of the TSPO activator, etifoxine. We extend those observations showing improvements in retinal pigment epithelial (RPE) cells with decreased lipids and enhanced expression of cholesterol metabolism and transport enzymes. Further, etifoxine decreased levels of reactive oxygen species (ROS) in RPE and inflammatory cytokines in RPE and serum. With respect to gut microbiome, we found that organisms abundant in the high fat condition (e.g. in the genus Anaerotruncus and Oscillospira) and implicated in AMD, were much less abundant after etifoxine treatment. The changes in gut flora were associated with the predicted production of metabolites of benefit to the retina including tryptophan and other amino acids and taurine, an essential component of the retina necessary to counteract ROS. These novel observations strengthen earlier conclusions that the mechanisms behind improvements in etifoxine-induced retinal physiology involve an interaction between effects on the host and the gut microbiome.
年龄相关性黄斑变性（AMD）是老年人视力损害的主要原因，其发病机制复杂，涉及遗传和环境因素，治疗选择有限，疗效有限。我们之前在高脂肪饮食诱导的小鼠模型中表明，TSPO 激活剂依非佐辛的联合给药可以逆转饮食的不良影响。我们进一步观察到，视网膜色素上皮（RPE）细胞中的脂质减少，胆固醇代谢和转运酶的表达增强，从而改善了 RPE 细胞。此外，依非佐辛降低了 RPE 中的活性氧（ROS）和 RPE 及血清中的炎症细胞因子的水平。关于肠道微生物组，我们发现高脂肪条件下丰富的（例如属 Anaerotruncus 和 Oscillospira）且与 AMD 相关的生物在依非佐辛治疗后数量明显减少。肠道菌群的变化与预测的有益于视网膜的代谢产物的产生有关，包括色氨酸和其他氨基酸以及牛磺酸，牛磺酸是对抗 ROS 所必需的视网膜的重要组成部分。这些新的观察结果进一步证实了之前的结论，即依非佐辛诱导的视网膜生理学改善的机制涉及宿主和肠道微生物组之间的相互作用。
