| First Author | Lin M | Year | 2012 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 53 |
| Issue | 10 | Pages | 6197-206 |
| PubMed ID | 22915031 | Mgi Jnum | J:213965 |
| Mgi Id | MGI:5586947 | Doi | 10.1167/iovs.11-8936 |
| Citation | Lin M, et al. (2012) Impacts of hypoxia-inducible factor-1 knockout in the retinal pigment epithelium on choroidal neovascularization. Invest Ophthalmol Vis Sci 53(10):6197-206 |
| abstractText | PURPOSE: Hypoxia-inducible factor (HIF)-1 is a key oxygen sensor and is believed to play an important role in neovascularization (NV). The purpose of this study is to determine the role of retinal pigment epithelium (RPE)-derived HIF-1alpha on ocular NV. METHODS: Conditional HIF-1alpha knockout (KO) mice were generated by crossing transgenic mice expressing Cre in the RPE with HIF-1alpha floxed mice, confirmed by immunohistochemistry, Western blot analysis, and fundus fluorescein angiography. The mice were used for the oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) models. RESULTS: HIF-1alpha levels were significantly decreased in the RPE layer of ocular sections and in primary RPE cells from the HIF-1alpha KO mice. Under normal conditions, the HIF-1alpha KO mice exhibited no apparent abnormalities in retinal histology or visual function as shown by light microscopy and electroretinogram recording, respectively. The HIF-1alpha KO mice with OIR showed no significant difference from the wild-type (WT) mice in retinal levels of HIF-1alpha and VEGF as well as in the number of preretinal neovascular cells. In the laser-induced CNV model, however, the disruption of HIF-1alpha in the RPE attenuated the over expression of VEGF and the intercellular adhesion molecule 1 (ICAM-1), and reduced vascular leakage and CNV area. CONCLUSIONS: RPE-derived HIF-1alpha plays a key role in CNV, but not in ischemia-induced retinal NV. |
