Seeing through VEGF: innate and adaptive immunity in pathological angiogenesis in the eye

Trends Mol Med. 2015 Jan;21(1):43-51. doi: 10.1016/j.molmed.2014.10.005. Epub 2014 Nov 1.

Abstract

The central role of vascular endothelial growth factor (VEGF) signaling in regulating normal vascular development and pathological angiogenesis has been documented in multiple studies. Ocular anti-VEGF therapy is highly effective for treating a subset of patients with blinding eye disorders such as diabetic retinopathy and neovascular age-related macular degeneration (AMD). However, chronic VEGF suppression can lead to adverse effects associated with poor visual outcomes due to the loss of prosurvival and neurotrophic capacities of VEGF. In this review, we discuss emerging evidence for immune-related mechanisms that regulate ocular angiogenesis in a VEGF-independent manner. These novel molecular and cellular pathways may provide potential therapeutic avenues for a multitarget strategy, preserving the neuroprotective functions of VEGF in those patients whose disease is unresponsive to VEGF neutralization.

Keywords: age-related macular degeneration (AMD); angiogenesis; diabetic retinopathy; immune regulation; neovascularization; vascular endothelial growth factor (VEGF).

Publication types

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

MeSH terms

  • Adaptive Immunity*
  • Animals
  • Eye / blood supply*
  • Eye / immunology
  • Eye / pathology
  • Eye Diseases / genetics
  • Eye Diseases / immunology*
  • Eye Diseases / pathology
  • Humans
  • Immunity, Innate*
  • Neovascularization, Pathologic
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / immunology*

Substances

  • Vascular Endothelial Growth Factor A