The YAP-Elevation Effect of Verteporfin in Retinal Non-Angiogenic Vessels Without Photodynamic Characteristics

Abstract

Purpose: Verteporfin (VP) is widely used in photodynamic therapy for retinal angiogenesis diseases. It also functions as a Yes-associated protein (YAP) antagonist in tumorigenesis. However, it has been implied that VP has multiple mechanisms in tumor cells and endothelial cells. In this study, we explore the effects of VP in retinal vessels. Methods: Blood samples were collected from patients receiving intravenous vp. Retinas were from mice after VP injection. Western blotting aimed to detect the levels of YAP and Hippo-related proteins in vivo and in vitro. The effect of VP was also tested in a retinopathy of prematurity model. Results: VP dramatically increased YAP and p-YAP levels in patient blood samples and mouse retinas. And YAP were decreased in the U87 cell line but increased in HUVECs. Retinal vascular leakage was significantly alleviated by VP, which similarly to YAP agonist. Conclusion: This study explored the novel effect of VP on YAP activation, and the results suggested tissue-specific effects of VP on YAP bioactivity. Our findings provide new insight into the effects of VP on non-angiogenic vessels without photodynamic characteristics, and VP may be a novel non-invasion therapeutic intervention for ROP. Funding Statement: This research was supported by the National Natural Science Foundation of China (No. 81570840 and No. 81371006), Academician Led Science and Technological Innovation of Chongqing (cstc2017jcyj-yszxX0006) and Research Foundation of Dept. Ophthalmology in Daping Hospital, AMU (No. 9-2543). Declaration of Interests: The authors declare there are no competing interests about this study. Ethics Approval Statement: The study was approved by the Ethics Research Committee of AMU (Permit Number: 2018-31), and all the participants provided informed consent before blood collection. The tenets of the Declaration of Helsinki were adhered to during all procedures of this study. All animal studies were performed in accordance with the ARVO Statement for Use of Animals in Ophthalmic and Vision Research and were approved by the Institutional Animal Care and Use Committee of the Army University.