Deciphering age-related transcriptomic changes in mouse retinal pigment epithelium

Aging of the retinal pigment epithelium (RPE) leads to a gradual decline in RPE homeostasis over time, significantly impacting retinal health. Understanding the mechanisms underlying RPE aging is crucial for elucidating the background in which many age-related retinal pathologies develop. In this study, we compared the transcriptomes of young and aged mouse RPE and found a marked upregulation of immunogenic and proinflammatory genes in aging RPE. Additionally, aging RPE exhibited dysregulation of pathways associated with visual perception and extracellular matrix production. Research on aging in post-natal quiescent RPE is hindered by the absence of relevant in vitro models. We evaluated an in vitro model of chronologically aged primary human RPE to address this gap, which displayed gene expression patterns comparable to native-aged RPE. Profiling this in vitro aging model highlighted its potential utility in investigating cellular and molecular mechanisms of RPE aging and in preliminary testing of therapeutic compounds. Overall, our findings suggest chronological aging of RPE leads to the acquisition of a proinflammatory phenotype, impacting RPE function and serving as a significant factor in the development of age-related retinal pathologies. Overall design: We performed transcriptome profiling of ribosomal RNA depleted sequencing data from RPE/choroid of young (2-3 months) and aged (20-24 months) mice (n=4 per group).