Subretinal fibrosis in neovascular age-related macular degeneration: current concepts, therapeutic avenues, and future perspectives

Cell Tissue Res. 2022 Mar;387(3):361-375. doi: 10.1007/s00441-021-03514-8. Epub 2021 Sep 3.

Abstract

Age-related macular degeneration (AMD) is a progressive, degenerative disease of the human retina which in its most aggressive form is associated with the formation of macular neovascularization (MNV) and subretinal fibrosis leading to irreversible blindness. MNVs contain blood vessels as well as infiltrating immune cells, myofibroblasts, and excessive amounts of extracellular matrix proteins such as collagens, fibronectin, and laminin which disrupts retinal function and triggers neurodegeneration. In the mammalian retina, damaged neurons cannot be replaced by tissue regeneration, and subretinal MNV and fibrosis persist and thus fuel degeneration and visual loss. This review provides an overview of subretinal fibrosis in neovascular AMD, by summarizing its clinical manifestations, exploring the current understanding of the underlying cellular and molecular mechanisms and discussing potential therapeutic approaches to inhibit subretinal fibrosis in the future.

Keywords: Age-related macular degeneration; Degenerative disease; Human retina; Subretinal fibrosis; choroidal neovascularization; macular neovascularization; scar formation.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors* / therapeutic use
  • Animals
  • Fibrosis
  • Humans
  • Mammals
  • Vascular Endothelial Growth Factor A
  • Visual Acuity
  • Wet Macular Degeneration* / drug therapy

Substances

  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor A