Choroidal neovascularization (CNV) is a prevalent cause of vision loss in patients with age-related macular degeneration. Runt-related transcription factor 1 (RUNX1) has been identified as an important mediator of aberrant retinal angiogenesis in proliferative diabetic retinopathy, and its modulation has proven to be effective curbing pathological angiogenesis in experimental oxygen-induced retinopathy. However, its role in CNV remains to be elucidated. This study demonstrates RUNX1 expression in critical cell types involved in laser-induced model of CNV in mice. Furthermore, we report the preclinical efficacy of Ro5-3335, a small molecule inhibitor of RUNX1, in experimental CNV. RUNX1 inhibitor Ro5-3335, aflibercept, an FDA-approved vascular endothelial growth factor (VEGF) inhibitor, or combination of both were administered by intravitreal injection immediately after laser injury. CNV area was evaluated by immunostaining with isolectin B4 of choroidal flatmounts, and vascular permeability was analyzed by fluorescein angiography. A single intravitreal injection of Ro5-3335 significantly decreased CNV area seven days after laser injury, and when combined with aflibercept, reduced vascular leakage more effectively than aflibercept alone. These data suggest that RUNX1 inhibition alone or in combination with anti-VEGF drugs could be a potential new therapy upon further clinical validation for patients suffering from neovascular age-related macular degeneration.
Copyright © 2020. Published by Elsevier Inc.

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