FGF21 Administration Suppresses Retinal and Choroidal Neovascularization in Mice

Cell Rep. 2017 Feb 14;18(7):1606-1613. doi: 10.1016/j.celrep.2017.01.014.

Abstract

Pathological neovascularization, a leading cause of blindness, is seen in retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. Using a mouse model of hypoxia-driven retinal neovascularization, we find that fibroblast growth factor 21 (FGF21) administration suppresses, and FGF21 deficiency worsens, retinal neovessel growth. The protective effect of FGF21 against neovessel growth was abolished in adiponectin (APN)-deficient mice. FGF21 administration also decreased neovascular lesions in two models of neovascular age-related macular degeneration: very-low-density lipoprotein-receptor-deficient mice with retinal angiomatous proliferation and laser-induced choroidal neovascularization. FGF21 inhibited tumor necrosis α (TNF-α) expression but did not alter Vegfa expression in neovascular eyes. These data suggest that FGF21 may be a therapeutic target for pathologic vessel growth in patients with neovascular eye diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration.

Keywords: FGF21; choroidal neovascularization; hypoxia; oxygen-induced retinopathy; retinal neovascularization.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Choroidal Neovascularization / drug therapy*
  • Choroidal Neovascularization / metabolism
  • Disease Models, Animal
  • Fibroblast Growth Factors / pharmacology*
  • Macular Degeneration / drug therapy
  • Macular Degeneration / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / metabolism
  • Retina / drug effects*
  • Retina / metabolism
  • Retinal Neovascularization / drug therapy*
  • Retinal Neovascularization / metabolism
  • Retinal Vessels / drug effects
  • Retinal Vessels / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • fibroblast growth factor 21
  • Fibroblast Growth Factors