Mechanisms of Aging Stress Retinal Cells, Contributing to Retinal Pathologies

As researchers here note, age-related diseases of the retina are age-related because underlying mechanisms of damage and dysfunction place stress on cells, changing their function and even killing them. Measuring changes in gene expression that take place in stressed cells is one way to look at these unfortunate effects, though it gives little insight into the fine details of why cell behavior changes. The various forms of damage and dysfunction that cause aging are fairly well catalogued, but it is presently unknown as to how they interact with one another in detail, and which of them is the most important in any given context. The easiest way to find out at present is to build a therapy that can address a form of damage, and test it in animal models.

Aging of the retinal pigment epithelium (RPE) leads to a gradual decline in RPE homeostasis over time, significantly impacting retinal health. During the physiological aging process, retinal tissues undergo functional decline and degeneration with the RPE serving as the primary site of damage in many age-related retinal diseases. While aging itself may not invariably lead to the onset of conditions such as age-related macular degeneration (AMD), retinitis pigmentosa (RP), and diabetic retinopathy (DR), age-related changes can predispose the eye to these diseases

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.