Deciphering age-related transcriptomic changes in the 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 observed a marked upregulation of immunogenic, proinflammatory, and oxidative stress 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. Here, we evaluated an in vitro model of chronologically aged primary human RPE to address this gap and observed gene expression patterns comparable to native-aged RPE. Gene expression profiling in this model highlighted its potential utility in investigating cellular and molecular mechanisms of RPE aging and in screening of therapeutic compounds. In conclusion, our findings underscore the pivotal role of inflammation, immune activation, and oxidative stress in the aging RPE landscape and provide insights into why age increases the risk of retinal pathologies.