Decreased Expression of Soluble Epoxide Hydrolase Suppresses Murine Choroidal Neovascularization.
Decreased Expression of Soluble Epoxide Hydrolase Suppresses Murine Choroidal Neovascularization.
复制标题
DOI：
10.3390/ijms232415595
复制
发表时间：
2022-12-09
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
新生血管性或“湿性”年龄相关性黄斑变性（nAMD）是老年人失明的主要原因。脉络膜新生血管（CNV）是nAMD的主要病理特征，其中来自脉络膜的异常新血管生长导致不可逆的视力丧失。迫切需要开发新的治疗策略来解决当前抗血管内皮生长因子生物制剂的局限性。以前，我们通过正向化学遗传学方法确定可溶性环氧化物水解酶（sEH）作为CNV的可能治疗靶点。本研究的目的是通过免疫组织化学和RNAscope原位杂交分别检测视网膜sEH蛋白和mRNA的表达来验证sEH作为靶点，并评估设计用于敲低sEH基因Ephx 2的腺相关病毒（AAV）载体在小鼠激光诱导的（L-）CNV模型中的功效。nAMD患者死后眼组织和鼠L-CNV显示sEH在光感受器和视网膜色素上皮细胞中过表达。Ephx 2敲低显著降低CNV和CNV相关炎症标记物的正常化mRNA表达水平。因此，本研究进一步确立了sEH作为针对与nAMD相关的CNV的有希望的治疗靶点。
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, 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.
登录
查看更多内容
影响因子：
4.4
作者：
Higgins, GT;Wang, JH;Redmond, HP
通讯作者：
Redmond, HP
影响因子：
3.7
作者：
Chen H;Liu B;Lukas TJ;Neufeld AH
通讯作者：
Neufeld AH
影响因子：
4.8
作者：
Amaratunga, A;Abraham, CR;Fine, RE
通讯作者：
Fine, RE
影响因子：
4.4
作者：
Capozzi, Megan E.;McCollum, Gary W.;Penn, John S.
通讯作者：
Penn, John S.
影响因子：
11.2
作者：
Gopinathan G;Milagre C;Pearce OM;Reynolds LE;Hodivala-Dilke K;Leinster DA;Zhong H;Hollingsworth RE;Thompson R;Whiteford JR;Balkwill F
通讯作者：
Balkwill F