Retinal G‐protein‐coupled receptor deletion exacerbates AMD ‐like changes via the PINK1 –parkin pathway under oxidative stress

作者：Yue Guo, Sitong Chen, Wenxue Guan, Ningda Xu, Li Zhu, Wei Du, Zhiming Liu, Hon W. Fong, Lvzhen Huang, Mingwei Zhao · 发表于：The FASEB Journal · 年份：2024 · DOI：10.1096/fj.202401160rr · 被引用次数：9 · 研究领域：Retinal Diseases and Treatments、Retinal Development and Disorders、Retinal Imaging and Analysis

The intake of high dietary fat has been correlated with the progression of age-related macular degeneration (AMD), affecting the function of the retinal pigment epithelium through oxidative stress. A high-fat diet (HFD) can lead to lipid metabolism disorders, excessive production of circulating free fatty acids, and systemic inflammation by aggravating the degree of oxidative stress. Deletion of the retinal G-protein-coupled receptor (RGR-d) has been identified in drusen. In this study, we investigated how the RGR-d exacerbates AMD-like changes under oxidative stress, both in vivo and in vitro. Fundus atrophy became evident, at 12 months old, particularly in the RGR-d + HFD group, and fluorescence angiography revealed narrower retinal vessels and a reduced perfusion area in the peripheral retina. Although rod electroretinography revealed decreasing trends in the a- and b-wave amplitudes in the RGR-d + HFD group at 12 months, the changes were not statistically significant. Mice in the RGR-d + HFD group showed a significantly thinner and more fragile retinal morphology than those in the WT + HFD group, with disordered and discontinuous pigment distribution in the RGR-d + HFD mice. Transmission electron microscopy revealed a thickened Bruch's membrane along the choriocapillaris endothelial cell wall in the RGR-d + HFD mice, and the outer nuclear layer structure appeared disorganized, with reduced nuclear density. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated...