Rajendran Sharmila, Narayansamy Angayarkanni, Annamalai Radha, Cruze Lawrence D, Kathiresan Purushothaman, Kuppan Kaviarasan
Department of Biomedical Sciences, Faculty of Biomedical Sciences & Technology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India.
Department of Biochemistry, Medical Research Foundation, Chennai, India.
Exp Eye Res. 2025 Feb;251:110178. doi: 10.1016/j.exer.2024.110178. Epub 2024 Nov 21.
Retinal pericytes (PCs) are contractile microvascular smooth muscle cells that wrap around the endothelial cells (ECs) maintaining intact retinal vasculature (RV) with a 1:1 ratio. Microvascular complications like diabetic retinopathy (DR) due to chronic diabetes causes apoptotic loss of PCs followed by diminished vessel stability, EC apoptosis, and ischemia, leading to retinal angiogenesis, and eventually severe vision loss. This study aimed to analyze the proteins in PCs isolated from the RV of diabetic human donor eyes and compare them with remaining mixed population (MP) of retinal vascular cells. PCs and MP proteomes were analyzed using semi-quantitative proteomics. Proteins were extracted, quantified, and analyzed in duplicate using LC-MS/MS on a Tandem mass spectrometer. Overall, 42 PC and 27 MP proteins, with 19 shared proteins, were identified. Functional enrichment analysis indicated that PC proteins share common biological processes, such as negative regulation of fibrinolysis and vLDL particle remodeling, nitric oxide transport, phospholipid efflux, positive control over the clearance of apoptotic cells, chondrocyte proliferation, lipoprotein lipase activity, and oxidative stress-induced intrinsic atrophic signaling pathways. In the fold enrichment analysis, the PC proteins were associated with cholesterol metabolism, Complement and coagulant, ECM-receptor interaction, longevity regulating pathway, Peroxisome proliferator-activated receptors (PPAR), focal adhesion and PI3 Akt signaling pathways. Among the PC proteins, vitronectin, gelsolin, hornerin, apolipoprotein A1, C3, H, and complement Factors C3, C4, and C9 were identified as the most highly ranked proteins in diabetes. The identified unique proteins of retinal PC could prove beneficial as a therapeutic target in the management of DR.
视网膜周细胞（PCs）是收缩性微血管平滑肌细胞，以1:1的比例包裹在内皮细胞（ECs）周围，维持视网膜血管系统（RV）的完整。慢性糖尿病引起的微血管并发症，如糖尿病视网膜病变（DR），会导致PCs凋亡性丧失，随后血管稳定性降低、ECs凋亡和缺血，进而导致视网膜血管生成，最终导致严重视力丧失。本研究旨在分析从糖尿病患者供体眼的RV中分离出的PCs中的蛋白质，并将其与视网膜血管细胞的剩余混合群体（MP）进行比较。使用半定量蛋白质组学分析PCs和MP蛋白质组。提取蛋白质、进行定量，并在串联质谱仪上使用LC-MS/MS进行一式两份分析。总体而言，共鉴定出42种PC蛋白和27种MP蛋白，其中有19种共享蛋白。功能富集分析表明，PC蛋白具有共同的生物学过程，如纤维蛋白溶解和极低密度脂蛋白颗粒重塑的负调控、一氧化氮转运、磷脂流出、凋亡细胞清除的正调控、软骨细胞增殖、脂蛋白脂肪酶活性以及氧化应激诱导的内在萎缩信号通路。在富集倍数分析中，PC蛋白与胆固醇代谢、补体和凝血、细胞外基质-受体相互作用、长寿调节途径、过氧化物酶体增殖物激活受体（PPAR）、粘着斑和PI3 Akt信号通路相关。在PC蛋白中，玻连蛋白、凝溶胶蛋白、角蛋白、载脂蛋白A1、C3、H以及补体因子C3、C4和C9被确定为糖尿病中排名最高的蛋白。所鉴定的视网膜PC独特蛋白可能被证明是治疗DR的有益治疗靶点。
