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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 over‐expression 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 β‐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. FASEB J. 33, 11194–11209 (2019). http://www.fasebj.org

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Hypoxia may cause abnormal proliferation and migration of the vascular smooth muscle cells (VSMCs) from the media to the intima. This contributes to vessel narrowing and accelerates the process of atherosclerosis. The association of the aberrant expression of long noncoding RNAs (lncRNAs) with the development and progression of atherosclerosis is well known; however, it is not well investigated in hypoxic VSMCs. Using a microarray approach, we identified 1056 and 2804 differentially expressed lncRNAs and mRNAs, respectively, in hypoxic and normoxic mouse aorta smooth muscle (MOVAS) cells. Of them, we randomly chose several lncRNAs and validated the microarray data using the quantitative PCR (qPCR) assay. Advanced bioinformatics analyses indicated that the up-regulated mRNAs were mainly involved in inflammatory responses, lipid metabolism, clearance of amyloid-β peptide, citrate cycle (TCA cycle), TGF-β signaling, and chemokine signaling. The down-regulated mRNAs were mainly involved in the apoptosis pathway, glycerolipid metabolism, Wnt signaling pathway, and MAPK signaling pathway. The constructed coexpression network indicated interactions between 87 lncRNAs and ten mRNAs. In addition, we demonstrated that the silence of lncRNA NONMMUT002434 expression could abrogate the migration and proliferation of smooth muscle cells dramatically. Our data provide comprehensive evidence on the differential expression of lncRNAs and mRNAs in hypoxic MOVAS cells, which may be valuable biomarkers for atherosclerotic diseases, and thereby facilitating diagnosis of atherosclerosis.