Plasma Proteomics to Identify Drug Targets and Potential Drugs for Retinal Artery Occlusion: An Integrated Analysis in the UK Biobank

Retinal artery occlusion (RAO), which is positively correlated
with acute ischemic stroke (IS) and results in severe visual impairment,
lacks effective intervention drugs. This study aims to perform integrated
analysis using UK Biobank plasma proteome data of RAO and IS to identify
potential targets and preventive drugs. A total of 7191 participants
(22 RAO patients, 1457 IS patients, 8 individuals with both RAO and
IS, and 5704 healthy age-gender-matched controls) were included in
this study. Unique 1461 protein expression profiles of RAO, IS, and
the combined data set, extracted from UK Biobank Plasma proteomics
projects, were analyzed using both differential expression analysis
and elastic network regression (Enet) methods to identify shared key
proteins. Subsequent analyses, including single cell type expression
assessment, pathway enrichment, and druggability analysis, were conducted
for verifying shared key proteins and discovery of new drugs. Five
proteins were found to be shared among the samples, with all of them
showing upregulation. Notably, adhesion G-protein coupled receptor
G1 (ADGRG1) exhibited high expression in glial cells of the brain
and eye tissues. Gene set enrichment analysis revealed pathways associated
with lipid metabolism and vascular regulation and inflammation. Druggability
analysis unveiled 15 drug candidates targeting ADGRG1, which demonstrated
protective effects against RAO, especially troglitazone (−8.5
kcal/mol). Our study identified novel risk proteins and therapeutic
drugs associated with the rare disease RAO, providing valuable insights
into potential intervention strategies.