Serine racemase deficiency attenuates choroidal neovascularization and reduces nitric oxide and VEGF levels by retinal pigment epithelial cells

• DOI: 10.1111/jnc.14214
• Publication Date: 2017-09-11T16:12:47Z
• Authors: Haiyan Jiang; Mengjuan Wu; Yimei Liu; Liping Song; Shifeng Li; Xianwei Wang; Yun‐feng Zhang; Junxu Fang; Shengzhou Wu
• Keywords: PEDF

Abstract Choroidal neovascularization ( CNV ) is a leading cause of blindness in age‐related macular degeneration. Production vascular endothelial growth factor VEGF and macrophage recruitment by retinal pigment epithelial cells RPE significantly contributes to the process an experimental model. Serine racemase SR expressed neurons glial cells, its product, d ‐serine, endogenous co‐agonist N ‐methyl‐ ‐aspartate receptor. Activation receptor results production nitric oxide . NO ), molecule that promotes choroidal neovascularization. These observations suggest possible roles With laser‐injured mice, we found inactivation ‐coding gene Srr null reduced volume, neovascular density, invading macrophages. We exploited underlying mechanism vivo ex from wild‐type WT mice To explore downstream target inactivation, showed choroid/ homogenates extracted contained less inducible synthase decreased phospho‐ VEGFR 2 compared amounts mice. In vitro , inflammation‐primed s more NOS, produced than did s. When co‐cultured with fewer RF /6A‐a cell line cell, migrated opposite side insert membrane pre‐treated Altogether, deficiency reduces response laser‐induced inflammatory stimuli, resulting cascade pro‐angiogenic cytokines, including recruitment, which contribute synergistically attenuated angiogenesis. image