Article Text

other Versions

PDF
Cytokines in neovascular age-related macular degeneration: fundamentals of targeted combination therapy
  1. João Rafael de Oliveira Dias,
  2. Eduardo Büchele Rodrigues,
  3. Mauricio Maia,
  4. Octaviano Magalhães Jr,
  5. Fernando Marcondes Penha,
  6. Michel Eid Farah
  1. Department of Ophthalmology, Vision Institute—IPEPO, Federal University of São Paulo, São Paulo, Brazil
  1. Correspondence to João Rafael de Oliveira Dias, Rua Napoleão de Barros 1098 ap 74, São Paulo 04024-003, Brazil; dias_joaor{at}yahoo.com.br

Abstract

The neovascular form of age-related macular degeneration (AMD), called wet-AMD or choroidal neovascularisation, begins with damage to the outer retinal cells and retinal pigment epithelium (RPE), which elicits a cascade of inflammatory and angiogenic responses leading to neovascularisation under the macula. Studies showed that oxidative damage, chronic inflammation of the RPE and complement misregulation work at different steps of this disease. After established neovascularisation, several pro- and antiangiogenic agents start to play an important role. Vascular endothelial growth factors (VEGFs) are the most specific and potent regulators of angiogenesis, which are inhibited by intravitreal injections of ranibizumab, bevacizumab, VEGF Trap, pegaptanib sodium and other agents under investigation. Pigment epithelium-derived factor, on the other hand, shows neuroprotective and antiangiogenic activities. Hepatocyte growth factor (HGF) has a mitogenic effect on a wide range of epithelial and endothelial cells, and it is inhibited by an anti-HGF monoclonal antibody. Platelet-derived growth factor is a potent chemoattractant and mitogen for both fibroblasts and retinal RPE cells, which has been inhibited experimentally by VEGF Trap and human anti-platelet-derived growth factor-D monoclonal antibody. Fibroblast growth factor-2 has pleiotropic effects in different cell and organ systems, and it is blocked by anti-FGF antibodies, with a greater benefit regarding antiangiogenesis when combined treatment with anti-VEGF is performed. Tumour necrosis factor alpha is expressed in the retina and the choroid, and its blockade in choroidal neovascularisation includes the use of monoclonals such as infliximab. This paper reviews the most important cytokines involved in the pathogenesis of wet-AMD, with emphasis on potential combined therapies for disease control.

  • Age-related macular degeneration (AMD)
  • choroidal neovascularisation (CNV)
  • cytokines
  • vascular endothelial growth factor (VEGF)
  • angiogenesis
  • choroid
  • retina
  • neovascularisation
  • pharmacology

Statistics from Altmetric.com

Footnotes

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.