Oral administration of CU06-1004 attenuates vascular permeability and stabilizes neovascularization in retinal vascular diseases
Minyoung Noh, Yeomyeong Kim, Haiying Zhang, Hyejeong Kim, Cho‐Rong Bae, Sunghye Lee, Young‐Guen Kwon
Abstract
Retinal vascular diseases are the leading cause of blindness worldwide. These diseases have common disease mechanisms including vascular endothelial growth factor (VEGF) signaling, hypoxia, and inflammation. Treatment of these diseases with laser therapy, anti-VEGF injections and/or steroids has significantly improved clinical outcomes. However, these strategies do not address the underlying cause of the pathology and may have harmful side effects. Pathological processes that damage retinal vessels result in vascular occlusion and impairment of the barrier properties of retinal endothelial cells, leading to excessive vascular leakage. Therefore, a new therapeutic approach is needed for the treatment of retinal vascular disease. We were able to confirm that oral administration of CU06-1004, an endothelial dysfunction blocker, inhibited retinal vascular leakage induced by vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang2). Interestingly, oral administration of CU06-1004 prevented excessive vascular leakage in the diabetic retinopathy model. In addition, CU06-1004 inhibited angiogenesis and confirmed vascular stabilization in the oxygen-induced retinopathy model and laser-induced CNV model. Taken together, CU06-1004 could be a potential therapeutic agent for the treatment of retinal vascular diseases.