Asymmetric dimethylarginine contributes to retinal neovascularization of diabetic retinopathy through EphrinB2 pathway

Vascular Pharmacology
Mei-Rong DuJun-Lin Jiang

Abstract

Diabetic retinopathy (DR) is a leading cause of vision loss with retinal neovascularization. This study aims to investigate whether Asymmetric dimethylarginine (ADMA) impacts the pathogenesis of DR via focusing on promoting retinal neovascularization and its underlying molecular mechanisms. Diabetic rats were induced by a single intraperitoneal injection of streptozotocin (STZ) for 20 weeks. ADMA levels in aqueous and the influence of hypoxia on ADMA and angiogenesis in RF/6A cells were examined. The effects and underlying molecular mechanisms of ADMA on neovascularization of RF/6A cells were further evaluated by administration of ADMA, DDAH siRNA or ephrinB2 siRNA. Results showed that ADMA levels were elevated in both aqueous from diabetic rats and culture medium in RF/6A cells pretreated with hypoxia. Administration of ADMA directly promoted proliferation, migration, adhesion and tube formation of RF/6A cells, which was further confirmed by DDAH1 siRNA or DDAH2 siRNA. In addition, ephrinB2 expression was increased under diabetic conditions, and the angiogenic effects of ADMA were blocked by ephrinB2 siRNA. In conclusion, ADMA contributes to the neovascularization of retina in diabetic mellitus, which is regulated by ephrinB2.

Citations

Sep 18, 2020·Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft·Ann K RosnerKatharina A Ponto
Oct 6, 2020·Frontiers in Endocrinology·Fu GuiYulan Zhang
Jul 3, 2021·International Journal of Molecular Sciences·Radoslaw KaczmarekMalgorzata Gajdzis
Jul 17, 2021·European Journal of Pharmacology·Li YanJun-Lin Jiang
Sep 30, 2021·American Journal of Ophthalmology·Katherine S PetersMilam A Brantley

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