The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD

Abstract

The retinal pigment epithelium (RPE) is a highly specialized, unique epithelial cell that interacts with photoreceptors on its apical side and with Bruch’s membrane and the choriocapillaris on its basal side. Due to vital functions that keep photoreceptors healthy, the RPE is essential for maintaining vision. With aging and the accumulated effects of environmental stresses, the RPE can become dysfunctional and die. This degeneration plays a central role in age-related macular degeneration (AMD) pathobiology, the leading cause of blindness among the elderly in western societies. Oxidative stress and inflammation have both physiological and potentially pathological roles in RPE degeneration. Given the central role of the RPE, this review will focus on the impact of oxidative stress and inflammation on the RPE with AMD pathobiology. Physiological sources of oxidative stress as well as unique sources from photo-oxidative stress, the phagocytosis of photoreceptor outer segments, and modifiable factors such as cigarette smoking and high fat diet ingestion that can convert oxidative stress into a pathological role, and the negative impact of impairing the cytoprotective roles of mitochondrial dynamics and the Nrf2 signaling system on RPE health in AMD will be discussed. Likewise, the response by the innate immune system to an inciting trigger, and the potential role of local RPE production of inflammation, as well as a potential role for damage by inflammation with chronicity if the inciting trigger is not neutralized, will be debated.

Effect of aging and lifestyle on photoreceptors and retinal pigment epithelium: cross-sectional study in a healthy Danish population

“…Smoking has a significant impact on both RPE cells and photoreceptors [32,33]. One example is that smoking leads to abnormal deposits in the RPE cells and disorganizes photoreceptors anatomically [33].…”

Oxidative Stress and Dysfunctional Intracellular Traffic Linked to an Unhealthy Diet Results in Impaired Cargo Transport in the Retinal Pigment Epithelium (RPE)

“…Their consumption is further linked with impaired long‐term potentiation and metabolic changes in the brain and degenerative conditions such as Age‐related Macular Degeneration (AMD) in which only genetic risk factors were once thought to be drivers of pathology. Dietary intake of such foods is associated with activation of major pathogenic pathways including oxidative stress, the intracellular accumulation and extracellular deposition of lipids and cholesterol as well as dysfunctional clearance mechanisms and chronic inflammation . Here, we focus on studying how high oxidative stress and deregulated intracellular trafficking creates an ideal environment for the development of retinal diseases.…”

Protective effects of microRNA‐22‐3p against retinal pigment epithelial inflammatory damage by targeting NLRP3 inflammasome

“…Oxidative stress has been strongly linked to RPE degeneration in AMD (Datta et al, ). High‐intensity light exposure is a mature method to induce oxidative retinopathy in mice, which has been described in our previous work (Fang et al, ).…”