ArticleInternational journal of ophthalmology2025
Integrating plasma proteomics and genome-wide association data to identify therapeutic targets for retinal neurodegenerative diseases in Europeans.
Article in International journal of ophthalmology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
aimTo employ proteome-wide Mendelian randomization (MR) to explore novel protein and drug targets for retinal neurodegenerative diseases (RND) in individuals of European ancestry.
methodsThis study used summary data-based MR to analyze the correlation between plasma protein levels and three RND, with protein data derived from two independent large-scale proteomics datasets. Potential drug targets were identified using Bayesian colocalization, followed by MR analysis, sensitivity testing, and external validation. Drug prediction and molecular docking were conducted to evaluate the druggability of the target proteins.
resultsThe study identified six promising protein targets, each successfully replicated at least twice. The results included three proteins related to diabetic retinopathy (ICAM1, GCKR, WARS), two proteins related to age-related macular degeneration (WARS, BRD2), and two proteins related to glaucoma (SVEP1, NPTXR). Additionally, drug prediction and molecular docking indicated that five drugs (fenofibrate, trofinetide, ticagrelor, lifitegrast, acetaminophen) effectively bound to the target proteins.
conclusionThis study identified six potential protein targets for RND and five existing drugs with therapeutic potential. By integrating plasma proteomics with genetic data, it provides a cost-effective framework for drug discovery.
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