Abstract
Purpose :
Neovascular age-related macular degeneration (AMD) is the major cause of irreversible vision loss in elderly population in developed countries. Introduction of intravitreal injection of anti-vascular endothelia growth factor agents has dramatically improved the treatment outcome in neovascular AMD. Yet, 5-10% of neovascular AMD patients lose visual acuity ≥15 letters despite treatment. Clec14a is a type I transmembrane protein which is endothelial cell-specific and has a key role in cell–cell contact in angiogenesis. Herein, we developed human antibody targeting C-type lectin-like domain of CLEC14a as a potential therapy for neovascular AMD. We aimed to investigate therapeutic potential of antibody targeting Clec14a (DeglycoC1) in a rat model of AMD
Methods :
Experimental choroidal neovascularization (CNV) was induced by laser photocoagulation in Brown Norway rats. Intravitreal injections of aflibercept (80 μg/2μL), DeglycoC1 (80 μg/2μL), and phosphate-buffered saline (2μL, control group) were performed on day 0 and 7. Seven days after injection, optical coherence tomography (OCT) and fluorescein angiography were performed in vivo to evaluate the thickness and leakage of CNV. Choroidal flat mount were also analyzed for the size of CNV. Ocular toxicity assessment was performed including intraocular pressure, electroretinography, and histology.
Results :
Time course analysis showed that the expression of Clec14a was up-regulated early after laser injury, but gradually decreased to baseline at 14 days. In treatment groups, mean area of CNV on flat mount and the proportion of CNV lesions with clinically significant fluorescein leakage significantly decreased compared with control when injected both on day 0 and 7. The CNV thickness by OCT or histology showed similar pattern. There was no ocular toxicity in deglycoC1 treated group.
Conclusions :
Clec14a is expressed on laser-induced CNV in the rat model, and intravitreal injection of antibody against Clec14a showed comparable effect with aflibercept in suppression of CNV formation and regression of preformed CNV. Clec14a may be a feasible treatment target for CNV in age-related macular degeneration.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.