biostudies-literaturePark BNEI NIH HHS15595https://www.ebi.ac.uk/biostudies/studies/S-EPMC9779010biostudies-literatureUnknown23(24)Neovascular 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, <i>Ephx2</i>, 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. <i>Ephx2</i> 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.International journal of molecular sciencesDecreased Expression of Soluble Epoxide Hydrolase Suppresses Murine Choroidal Neovascularization.PMC9779010R01EY031939R01 EY025641R01EY025641R01 EY031939Sishtla KLSardar Pasha SPBHartman GDQi XCorson TWPark BBoulton MEfalseDecreased Expression of Soluble Epoxide Hydrolase Suppresses Murine Choroidal Neovascularization.Neovascular 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, <i>Ephx2</i>, 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. <i>Ephx2</i> 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.2022-01-01T00:00:00Z2022 Dec2025-04-04T08:45:30.751Z2025-04-04T08:45:30.751ZS-EPMC97790103655523610.3390/ijms232415595