Gene transfer for neovascular age-related macular degeneration

Hum Gene Ther. 2011 May;22(5):523-9. doi: 10.1089/hum.2011.050.


Age-related macular degeneration (AMD) is a complex disease that has two phases: a degenerative phase often referred to as nonneovascular AMD (non-NVAMD) or dry AMD and a phase dominated by growth of new blood vessels in the subretinal space, referred to as NVAMD or wet AMD. Advances in the understanding of the molecular pathogenesis of NVAMD have led to new drug therapies that have provided major benefits to patients. However, those treatments require frequent intraocular injections that in many patients must be continued indefinitely to maintain visual benefits. Gene transfer to augment expression of endogenous antiangiogenic proteins is an alternative approach that has the potential to provide long-term stability in patients with NVAMD. Studies in animal models that mimic aspects of NVAMD have identified several possible transgenes, and a clinical trial in patients with advanced NVAMD has suggested that the approach may be feasible. Many important questions remain, but the rationale and preliminary data are compelling. The results of two ongoing clinical trials may answer several of the questions and help direct future research.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Angiogenesis Inhibitors / metabolism*
  • Angiostatins / administration & dosage
  • Angiostatins / pharmacology
  • Dependovirus
  • Endostatins / administration & dosage
  • Endostatins / pharmacology
  • Eye Proteins / administration & dosage
  • Eye Proteins / pharmacology
  • Gene Expression Regulation / drug effects*
  • Gene Transfer Techniques*
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Humans
  • Nerve Growth Factors / administration & dosage
  • Nerve Growth Factors / pharmacology
  • Serpins / administration & dosage
  • Serpins / pharmacology
  • Vascular Endothelial Growth Factor Receptor-1 / administration & dosage
  • Vascular Endothelial Growth Factor Receptor-1 / pharmacology
  • Wet Macular Degeneration / physiopathology*
  • Wet Macular Degeneration / therapy*


  • Angiogenesis Inhibitors
  • Endostatins
  • Eye Proteins
  • Nerve Growth Factors
  • Serpins
  • pigment epithelium-derived factor
  • Angiostatins
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1