Epigenetic Regulation of Retinal Pigment Epithelium Dysfunction in Age-Related Macular Degeneration: Insights from a Nigerian Case-Control Study

The retinal pigment epithelium (RPE) plays a central role in maintaining photoreceptor health, and its progressive dysfunction underlies the pathogenesis of age-related macular degeneration (AMD). Epigenetic modifications, particularly DNA methylation and histone acetylation, have been implicated in RPE senescence and AMD development in European populations, but analogous data from African populations are entirely absent. This study investigates epigenetic regulation of RPE-related gene expression in Nigerian AMD patients using a case-control biomarker design at Lagos University Teaching Hospital and University College Hospital Ibadan, South West Nigeria. Thirty AMD cases confirmed by multimodal retinal imaging and 30 controls will contribute peripheral blood samples for genome-wide methylation profiling using the Infinium MethylationEPIC array, supplemented by RPE-relevant gene expression analysis via quantitative PCR. Differential methylation analysis will identify AMD-associated epigenetic signatures, with pathway analysis using gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Candidate epigenetic biomarkers will be correlated with AMD staging and clinical severity parameters. This study constitutes an original mechanistic investigation of AMD epigenetics in an African population, contributing novel data to the global AMD pathogenesis literature. Findings will be published in journals specializing in ophthalmic genetics and submitted to the International AMD Genetics Consortium for meta-analytic integration. Keywords: epigenetics, retinal pigment epithelium, age-related macular degeneration, DNA methylation, Nigeria