Diabetic retinopathy from the vitreous proteome perspective: The INStransgenic pig model study.

Abstract

INStransgenic pigs represent a model for mutant insulin gene-induced diabetes of youth, with impaired insulin secretion and beta cell loss, leading to elevated fasting blood glucose levels. A key complication of diabetes mellitus is diabetic retinopathy (DR), characterized by hyperglycemia-induced abnormalities in the retina. Adjacent to the retina lies the vitreous, a gelatinous matrix vital for ocular function. It harbors proteins and signaling molecules, offering insights into vitreous biology and ocular health. Moreover, as a reservoir for secreted molecules, the vitreous illuminates molecular processes within intraocular structures, especially under pathological conditions. To uncover the proteomic profile of porcine vitreous and explore its relevance to DR, we employed discovery proteomics to compare vitreous samples from INStransgenic pigs and wild-type controls. Our analysis identified 1404 proteins, with 266 showing differential abundance in INSvitreous. Notably, the abundances of ITGB1, COX2, and GRIFIN were significantly elevated in INSvitreous. Gene Set Enrichment Analysis unveiled heightened MYC and mTORC1 signaling in INSvitreous, shedding light on its biological significance in diabetes-associated ocular pathophysiology. These findings deepen our understanding of vitreous involvement in DR and provide valuable insights into potential therapeutic targets. Raw data are accessible via ProteomeXchange (PXD038198).