Inhibition of ocular neovascularization by novel anti-angiogenic compound. (December 2021)

• Record Type: Journal Article
• Authors: Gau, David; Vignaud, Lucile; Francoeur, Paul; Koes, David; Guillonneau, Xavier; Roy, Partha
• Is Part Of: Experimental eye research. Volume 213(2021)
• Publication Date: 2021-12
• Subjects: AMD Age-related macular degeneration -- Pfn1 Profilin1 -- CNV choroidal neovascularization -- IVT intravitreal -- SAR structure-activity relationship -- VEC Vascular Endothelial cells -- HdmVEC Human dermal microvascular endothelial cells -- HrmVEC Human retinal microvascular endothelial cells -- VEGF vascular endothelial growth factor; Angiogenesis -- AMD -- Profilin -- Actin -- Small molecule compound; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2021.108861
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: Aberrant angiogenesis lies at the heart of a wide range of ocular pathologies such as proliferative diabetic retinopathy, wet age-related macular degeneration and retinopathy of prematurity. This study explores the anti-angiogenic activity of a novel small molecule investigative compound capable of inhibiting profilin1-actin interaction recently identified by our group. We demonstrate that our compound is capable of inhibiting migration, proliferation and angiogenic activity of microvascular endothelial cells in vitro as well as choroidal neovascularization (CNV) ex vivo . In mouse model of laser-injury induced CNV, intravitreal administration of this compound diminishes sub-retinal neovascularization. Finally, our preliminary structure-activity relationship study (SAR) demonstrates that this small molecule compound is amenable to improvement in biological activity through structural modifications.