Proteome of pericytes from retinal vasculature of diabetic donor eyes

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 followe...

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Veröffentlicht in:Experimental eye research 2025-02, Vol.251, p.110178, Article 110178
Hauptverfasser: Rajendran, Sharmila, Narayansamy, Angayarkanni, Annamalai, Radha, Cruze, Lawrence D., Kathiresan, Purushothaman, Kuppan, Kaviarasan
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Sprache:eng
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Zusammenfassung: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. •This is the first report of diabetic retinal pericytes isolated from the retinal vasculature using the immunopanning method.•Diabetic retinal pericyte proteins,identified in this study can be used as potential therapeutic targets or drugs to treat diabetic retinopathy.•This is the first document reveals that diabetic retinal pericytes express hornerin protein.
ISSN:0014-4835
1096-0007
1096-0007
DOI:10.1016/j.exer.2024.110178