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Anthony Abraham Jones, Joshua L. Morgenstern, Anne D. Strong, Jeffrey Olson; A Novel Surrobody Reduces Neovascularization in a Rat Model of CNV. Invest. Ophthalmol. Vis. Sci. 2019;60(9):132.
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© ARVO (1962-2015); The Authors (2016-present)
Chorodial neovascularization (CNV) is the leading cause of severe vision loss in patients with age-related macular degeneration (AMD). CNV is believed to be the result of vascular endothelial growth factor (VEGF) upregulation. VEGF binds to VEGF receptors on endothelial cells in the choroid, generating abnormal growth and migration through the retina with blood vessel recruitment. Current CNV therapies, including afilbercept, target only VEGF in management of CNV. Angiopoietin 2 (ANG2), another proangiogenic cytokine, has been found to be elevated in patients with AMD and correlated with increased disease severity. The aim of this study was to assess and compare the therapeutic efficacy of SL-634 (surrobody), a bispecific inhibitor for VEGF and ANG2, to aflibercept in vivo by inducing CNV in a rat model.
Surrobody was first evaluated for retinal toxicity by retinal histology and electroretinography (n=5). CNV was then induced by laser photocoagulation in Brown Norway rats (n=10). Surrobody, afilbercept, or balanced salt solution (BSS) was administered through intravitreal injection immediately following injury. Injections were repeated seven days later and eyes were harvested fourteen days after initial insult. CNV area was then measured in choroid flat mounts and masked analysis was performed with a computer-assisted imaging program. Statistical analysis was performed using f-test and one-way ANOVA.
Intravitreal injection of surrobody showed no signs of retinal toxicity via electrophysiological or structural abnormalities. CNV area was decreased by 60% and 53% in eyes receiving surrobody and afilbercept treatment, respectively, compared to the BSS administration (p=.0015, one-way ANOVA). Reduction of CNV area in surrobody treated eyes was found to be statistically superior compared to afilbercept treatment (p=.028, f-test)
These results indicate that administration of surrobody, targeting VEGF and ANG2, was associated with increased reduction of CNV compared to afilbercept and should be further validated for treatment of neovascular AMD.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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