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Proteome atlas for mechanistic discovery and risk prediction of diabetic retinopathy
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DOI：10.1038/s41467-025-64634-1.png)
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Abstract
En 中文
Proteomics offers an unprecedented opportunity to characterize and predict diabetic retinopathy (DR) with minimal invasiveness. Here we examine this in 10,873 individuals with (pre)diabetes from two ethnically distinct cohorts. By simultaneous profiling of ~3000 proteins, we identify 668 associations with mechanistically plausible directionality that constitute a comprehensive DR proteomic landscape with linkages to retinal tomographic structure and genetic predisposition, pointing to established and novel biological pathways conferring DR risk. Integrating DR proteomic profile markedly improves predictive performance beyond clinical and genetic predictors, with plexin B2, growth differentiation factor 15, and renin emerging as top proteins validated across cohorts and linked to retinal microvascular degeneration in Guangzhou Diabetic Eye Study (GDES) based on SS-OCTA. A parsimonious panel of these three proteins alone achieves comparable performance in predicting DR development and progression, while renin is confirmed as a causal promoter through genetic analyses. Our findings highlight the potential of large-scale proteomics in elucidating DR pathogenesis and advancing biomarker discovery, with broad implications for early detection and intervention. Diabetic retinopathy is a major cause of blindness, yet ways to predict who will be affected remain limited. Here, the authors show that patterns of blood proteins can reveal disease mechanisms and enable powerful early prediction across diverse populations.
Keywords:
diabetic retinopathy
proteomics
biomarker discovery
risk prediction
protein profiling
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