期刊
JOURNAL OF MOLECULAR NEUROSCIENCE
卷 56, 期 1, 页码 78-88出版社
HUMANA PRESS INC
DOI: 10.1007/s12031-014-0469-2
关键词
R59949; PHD-2; Neovascularization; HIF-1 alpha; VEGF; Astrocytes; Oxygen-induced retinopathy
资金
- National Natural Science Foundation of China [81470030]
- Specialized Research Foundation for Doctoral Program of Higher Education [20120171110086]
- Science and Technology Planning Project of Guangzhou [11C22060787]
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.
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