An integrated bioinformatics analysis identifying ALOX15 as a novel pharmacological target for retinitis pigmentosa and diabetic retinopathy

This study aimed to find shared gene signatures, molecular processes, and potential pharmacological targets in retinitis pigmentosa (RP) and diabetic retinopathy (DR) through integrated bioinformatics analysis. Two datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes were identified using the R software, and co-expression gene weighted expression method (WGCNA) was conducted to find the co-expression networks. Common genes were screened with a Venn tool. Functional and pathway enrichment analyses were performed, and a protein-protein interaction (PPI) network was constructed. Common miRNAs were identified and functionally analyzed. Seven overlapping differentially expressed genes and 2 shared genes from WGCNA core modules were identified. Gene Ontology (GO) analysis highlighted regulation of lipoxin metabolism and membrane-associated oxidoreductase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment focused on linoleic and arachidonic acid metabolism, with ALOX15 as the key oxidase. PPI network analysis also emphasized ALOX15. The overlapping miRNA hsa-mir-133b was associated with organelle-related functions. Integrated bioinformatics revealed that the lipoxygenase pathway and membrane oxidoreductase activity likely contribute to RP and DR pathogenesis, with ALOX15 as a promising therapeutic target. ALOX15's role in lipoxin metabolism and oxidative stressed positions it as a novel pharmacological target for preserving retinal function in RP and DR. These findings paved the way for developing targeted therapies to improve visual outcomes in these diseases.