Diacylglycerol Kinase (DGK) Inhibitor II (R59949) Could Suppress Retinal Neovascularization and Protect Retinal Astrocytes in an Oxygen-Induced Retinopathy Model

Hypoxia-inducible factors (HIF) play a fundamental role in retinal neovascularization (NV) induced by low oxygen tension. In the presence of oxygen, the HIF-alpha subunit becomes hydroxylated at specific prolyl residues by prolyl hydroxylases (PHD), which triggers HIF-alpha for degradation. In our present study, we examined the effect of R59949, the diacylglycerol kinase (DGK) inhibitor II, on the retinal NV and its potential mechanism in an oxygen-induced retinopathy (OIR) model. OIR model was induced by exposure of hyperoxia (75 % oxygen) to C57BL/6J mice from postnatal day 7 (P7) to P12 and then returned to room air. By intraperitoneal injection once a day (10 mu g/g/day) from P12 to P17, R59949 not only effectively prevented pathologic NV but also preserved the astrocyte morphology. Furthermore, the expression of PHD-2 was upregulated and HIF-1 alpha and vascular endothelial growth factor (VEGF) were downregulated in the retina of OIR mice following R59949 treatment. These findings suggested a potential possibility that R59949 suppressed retinal neovascular pathophysiology via PHD2/HIF-1 alpha/VEGF pathway.