The effects of endothelium-specific CYP2J2 overexpression on the attenuation of retinal ganglion cell apoptosis in a glaucoma rat model
The effects of endothelium-specific CYP2J2 overexpression on the attenuation of retinal ganglion cell apoptosis in a glaucoma rat model
复制标题
内皮特异性 CYP2J2 过表达对青光眼大鼠模型视网膜神经节细胞凋亡减弱的影响。
DOI：
10.1096/fj.201900756r
复制
发表时间：
2019-10-01
期刊：
影响因子：
4.8
通讯作者：
Zhang, Hong
中科院分区：
文献类型：
--
作者：
Huang, Jingqiu;Zhao, Qinshuo;Zhang, Hong
青光眼是世界范围内导致不可逆失明的主要原因。血管因素在青光眼的发病机制中起重要作用。细胞色素P450 (CYP) 2J2表达于血管内皮，是代谢花生四烯酸生成环氧二碳三烯酸的CYP加氧酶之一，对血管系统具有多效保护作用。在本研究中，我们研究了内皮特异性过表达CYP2J2 （tie2-CYP2J2-Tr）是否能保护青光眼引起的视网膜神经节细胞（RGC）损失，以及视网膜血管以何种方式参与这一过程。我们采用大鼠视网膜缺血再灌注（I/R）损伤青光眼模型，发现内皮特异性过表达CYP2J2可减轻视网膜I/R引起的RGC损失。此外，视网膜I/R触发视网膜血管衰老，表现为衰老相关蛋白p53、p16和β -半乳糖苷酶活性上调。内皮细胞衰老导致周细胞丢失，内皮细胞分泌基质金属肽酶9增加，进一步导致RGC丢失。CYP2J2过表达可减轻血管衰老、周细胞损失和基质金属肽酶9分泌。CYP2J2通过下调衰老相关蛋白p53和p16抑制内皮细胞衰老。这两种蛋白均受microRNA-128-3p的正调控，而CYP2J2则对其抑制。这些结果表明CYP2J2可以防止青光眼的内皮衰老和RGC丢失，这一发现可能会导致青光眼治疗策略的发展。-黄洁，赵强，李敏，段强，赵艳，张华，张华。内皮特异性CYP2J2过表达对青光眼大鼠视网膜神经节细胞凋亡衰减的影响。
Glaucoma is a leading cause of irreversible blindness worldwide. Vascular factors play a substantial role in the pathogenesis of glaucoma. Expressed in the vascular endothelium, cytochrome P450 (CYP) 2J2 is one of the CYP epoxygenases that metabolize arachidonic acid to produce epoxyeicosatrienoic acids and exert pleiotropic protective effects on the vasculature. In the present study, we investigated whether endothelium-specific overexpression of CYP2J2 (tie2-CYP2J2-Tr) protects against retinal ganglion cell (RGC) loss induced by glaucoma and in what way retinal vessels are involved in this process. We used a glaucoma model of retinal ischemia-reperfusion (I/R) injury in rats and found that endothelium-specific overexpression of CYP2J2 attenuated RGC loss induced by retinal I/R. Moreover, retinal I/R triggered retinal vascular senescence, indicated by up-regulated senescence-related proteins p53, p16, and beta-galactosidase activity. The senescent endothelial cells resulted in pericyte loss and increased endothelial secretion of matrix metallopeptidase 9, which further contributed to RGC loss. CYP2J2 overexpression alleviated vascular senescence, pericyte loss, and matrix metallopeptidase 9 secretion. CYP2J2 suppressed endothelial senescence by down-regulating senescence-associated proteins p53 and p16. These 2 proteins were positively regulated by microRNA-128-3p, which was inhibited by CYP2J2. These results suggest that CYP2J2 protects against endothelial senescence and RGC loss in glaucoma, a discovery that may lead to the development of a potential treatment strategy for glaucoma.-Huang, J., Zhao, Q., Li, M., Duan, Q., Zhao, Y., Zhang, H. The effects of endothelium-specific CYP2J2 overexpression on the attenuation of retinal ganglion cell apoptosis in a glaucoma rat model.