title: Gene Therapy with Endogenous Inhibitors of Angiogenesis for Neovascular Age-Related Macular Degeneration: Beyond Anti-VEGF Therapy.
abstract: 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.
authors.affiliation: Department of Optometry & Vision Sciences, University of Melbourne, 4th Floor, Alice Hoy Building, 162 Monash Road, Parkville, VIC 3010, Australia ; Centre for Eye Research Australia, Level 1, 32 Gisborne Street, East Melbourne, VIC 3002, Australia.
authors.forename: Selwyn M
authors.initials: SM
authors.lastname: Prea
authors.affiliation: Centre for Eye Research Australia, Level 1, 32 Gisborne Street, East Melbourne, VIC 3002, Australia ; Department of Ophthalmology, University of Melbourne, Level 1, 32 Gisborne Street, East Melbourne, VIC 3002, Australia.
authors.forename: Elsa C
authors.initials: EC
authors.lastname: Chan
authors.affiliation: Centre for Eye Research Australia, Level 1, 32 Gisborne Street, East Melbourne, VIC 3002, Australia ; Department of Ophthalmology, University of Melbourne, Level 1, 32 Gisborne Street, East Melbourne, VIC 3002, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dusting
authors.affiliation: Department of Optometry & Vision Sciences, University of Melbourne, 4th Floor, Alice Hoy Building, 162 Monash Road, Parkville, VIC 3010, Australia.
authors.forename: Algis J
authors.initials: AJ
authors.lastname: Vingrys
authors.affiliation: Department of Optometry & Vision Sciences, University of Melbourne, 4th Floor, Alice Hoy Building, 162 Monash Road, Parkville, VIC 3010, Australia.
authors.forename: Bang V
authors.initials: BV
authors.lastname: Bui
authors.affiliation: Centre for Eye Research Australia, Level 1, 32 Gisborne Street, East Melbourne, VIC 3002, Australia ; Department of Ophthalmology, University of Melbourne, Level 1, 32 Gisborne Street, East Melbourne, VIC 3002, Australia.
authors.forename: Guei-Sheung
authors.identifier: 0000-0003-3379-724X
authors.initials: GS
authors.lastname: Liu
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