Novel Programmed Cell Death as Therapeutic Targets in Age-Related Macular Degeneration?

Int J Mol Sci. 2020 Oct 1;21(19):7279. doi: 10.3390/ijms21197279.

Abstract

Age-related macular degeneration (AMD) is a leading cause of severe visual loss among the elderly. AMD patients are tormented by progressive central blurring/loss of vision and have limited therapeutic options to date. Drusen accumulation causing retinal pigment epithelial (RPE) cell damage is the hallmark of AMD pathogenesis, in which oxidative stress and inflammation are the well-known molecular mechanisms. However, the underlying mechanisms of how RPE responds when exposed to drusen are still poorly understood. Programmed cell death (PCD) plays an important role in cellular responses to stress and the regulation of homeostasis and diseases. Apart from the classical apoptosis, recent studies also discovered novel PCD pathways such as pyroptosis, necroptosis, and ferroptosis, which may contribute to RPE cell death in AMD. This evidence may yield new treatment targets for AMD. In this review, we summarized and analyzed recent advances on the association between novel PCD and AMD, proposing PCD's role as a therapeutic new target for future AMD treatment.

Keywords: cell damage; homeostasis; ocular stress; retina; vision.

Publication types

  • Review

MeSH terms

  • Aging / genetics*
  • Aging / metabolism
  • Aging / pathology
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Bevacizumab / therapeutic use
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Ferroptosis / drug effects*
  • Ferroptosis / genetics
  • Humans
  • Macular Degeneration / genetics
  • Macular Degeneration / metabolism
  • Macular Degeneration / pathology
  • Macular Degeneration / therapy*
  • Necroptosis / drug effects*
  • Necroptosis / genetics
  • Oxidative Stress
  • Photochemotherapy / methods
  • Photosensitizing Agents / therapeutic use
  • Pyroptosis / drug effects*
  • Pyroptosis / genetics
  • Ranibizumab / therapeutic use
  • Retinal Drusen / genetics
  • Retinal Drusen / metabolism
  • Retinal Drusen / pathology
  • Retinal Drusen / therapy*
  • Retinal Pigment Epithelium / drug effects
  • Retinal Pigment Epithelium / metabolism
  • Retinal Pigment Epithelium / pathology
  • Stem Cell Transplantation / methods
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Verteporfin / therapeutic use

Substances

  • Photosensitizing Agents
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Verteporfin
  • Bevacizumab
  • Ranibizumab