Park, BominaSardar Pasha, Sheik Pran BabuSishtla, Kamakshi L.Hartman, Gabriella D.Qi, XiaopingBoulton, Michael E.Corson, Timothy W.2023-03-292023-03-292022-12Park, B., Sardar Pasha, S. P. B., Sishtla, K. L., Hartman, G. D., Qi, X., Boulton, M. E., & Corson, T. W. (2022). Decreased Expression of Soluble Epoxide Hydrolase Suppresses Murine Choroidal Neovascularization. International Journal of Molecular Sciences, 23(24), 15595. https://doi.org/10.3390/ijms232415595https://hdl.handle.net/1805/32102Neovascular or “wet” age-related macular degeneration (nAMD) is a leading cause of blindness among older adults. Choroidal neovascularization (CNV) is a major pathological feature of nAMD, in which abnormal new blood vessel growth from the choroid leads to irreversible vision loss. There is a critical need to develop novel therapeutic strategies to address limitations of the current anti-vascular endothelial growth factor biologics. Previously, we identified soluble epoxide hydrolase (sEH) as a possible therapeutic target for CNV through a forward chemical genetic approach. The purpose of this study was to validate sEH as a target by examining retinal expression of sEH protein and mRNA by immunohistochemistry and RNAscope in situ hybridization, respectively, and to assess the efficacy of an adeno-associated virus (AAV) vector designed to knock down the sEH gene, Ephx2, in the murine laser-induced (L-) CNV model. nAMD patient postmortem eye tissue and murine L-CNV showed overexpression of sEH in photoreceptors and retinal pigment epithelial cells. Ephx2 knockdown significantly reduced CNV and normalized mRNA expression levels of CNV-related inflammatory markers. Thus, this study further establishes sEH as a promising therapeutic target against CNV associated with nAMD.enAttribution 4.0 Internationaladenoassociated viral vectorchoroidal neovascularizationneovascular age-related macular degenerationArticle