Autophagy in dry AMD: A promising therapeutic strategy for retinal pigment epithelial cell damage

Exp Eye Res. 2024 May:242:109889. doi: 10.1016/j.exer.2024.109889. Epub 2024 Apr 7.

Abstract

Dry age-related macular degeneration (AMD) is a prevalent clinical condition that leads to permanent damage to central vision and poses a significant threat to patients' visual health. Although the pathogenesis of dry AMD remains unclear, there is consensus on the role of retinal pigment epithelium (RPE) damage. Oxidative stress and chronic inflammation are major contributors to RPE cell damage, and the NOD-like receptor thermoprotein structural domain-associated protein 3 (NLRP3) inflammasome mediates the inflammatory response leading to apoptosis in RPE cells. Furthermore, lipofuscin accumulation results in oxidative stress, NLRP3 activation, and the development of vitelliform lesions, a hallmark of dry AMD, all of which may contribute to RPE dysfunction. The process of autophagy, involving the encapsulation, recognition, and transport of accumulated proteins and dead cells to the lysosome for degradation, is recognized as a significant pathway for cellular self-protection and homeostasis maintenance. Recently, RPE cell autophagy has been discovered to be closely linked to the development of macular degeneration, positioning autophagy as a cutting-edge research area in the realm of dry AMD. In this review, we present an overview of how lipofuscin, oxidative stress, and the NLRP3 inflammasome damage the RPE through their respective causal mechanisms. We summarized the connection between autophagy, oxidative stress, and NLRP3 inflammatory cytokines. Our findings suggest that targeting autophagy improves RPE function and sustains visual health, offering new perspectives for understanding the pathogenesis and clinical management of dry AMD.

Keywords: Autophagy; Dry age-related macular degeneration; Lipofuscin; NLRP3 inflammasome; Oxidative stress; mTOR.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy* / physiology
  • Geographic Atrophy / metabolism
  • Geographic Atrophy / pathology
  • Humans
  • Inflammasomes / metabolism
  • Lipofuscin / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Oxidative Stress* / physiology
  • Retinal Pigment Epithelium* / metabolism
  • Retinal Pigment Epithelium* / pathology

Substances

  • Inflammasomes
  • Lipofuscin
  • NLR Family, Pyrin Domain-Containing 3 Protein