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Journal of Ophthalmology
Volume 2015 (2015), Article ID 201726, 12 pages
Review Article

Gene Therapy with Endogenous Inhibitors of Angiogenesis for Neovascular Age-Related Macular Degeneration: Beyond Anti-VEGF Therapy

1Department of Optometry & Vision Sciences, University of Melbourne, 4th Floor, Alice Hoy Building, 162 Monash Road, Parkville, VIC 3010, Australia
2Centre for Eye Research Australia, Level 1, 32 Gisborne Street, East Melbourne, VIC 3002, Australia
3Department of Ophthalmology, University of Melbourne, Level 1, 32 Gisborne Street, East Melbourne, VIC 3002, Australia

Received 12 June 2014; Accepted 8 September 2014

Academic Editor: Petros E. Carvounis

Copyright © 2015 Selwyn M. Prea et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Age-related macular degeneration (AMD) is the leading cause of substantial and irreversible vision loss amongst elderly populations in industrialized countries. The advanced neovascular (or “wet”) form of the disease is responsible for severe and aggressive loss of central vision. Current treatments aim to seal off leaky blood vessels via laser therapy or to suppress vessel leakage and neovascular growth through intraocular injections of antibodies that target vascular endothelial growth factor (VEGF). However, the long-term success of anti-VEGF therapy can be hampered by limitations such as low or variable efficacy, high frequency of administration (usually monthly), potentially serious side effects, and, most importantly, loss of efficacy with prolonged treatment. Gene transfer of endogenous antiangiogenic proteins is an alternative approach that has the potential to provide long-term suppression of neovascularization and/or excessive vascular leakage in the eye. Preclinical studies of gene transfer in a large animal model have provided impressive preliminary results with a number of transgenes. In addition, a clinical trial in patients suffering from advanced neovascular AMD has provided proof-of-concept for successful gene transfer. In this mini review, we summarize current theories pertaining to the application of gene therapy for neovascular AMD and the potential benefits when used in conjunction with endogenous antiangiogenic proteins.