| First Author | Madamanchi A | Year | 2014 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 55 |
| Issue | 7 | Pages | 4338-47 |
| PubMed ID | 24917135 | Mgi Jnum | J:230100 |
| Mgi Id | MGI:5755374 | Doi | 10.1167/iovs.14-14061 |
| Citation | Madamanchi A, et al. (2014) Mitigation of oxygen-induced retinopathy in alpha2beta1 integrin-deficient mice. Invest Ophthalmol Vis Sci 55(7):4338-47 |
| abstractText | PURPOSE: The alpha2beta1 integrin plays an important but complex role in angiogenesis and vasculopathies. Published GWAS studies established a correlation between genetic polymorphisms of the alpha2beta1 integrin gene and incidence of diabetic retinopathy. Recent studies indicated that alpha2-null mice demonstrate superior vascularization in both the wound and diabetic microenvironments. The goal of this study was to determine whether the vasculoprotective effects of alpha2-integrin deficiency extended to the retina, using the oxygen-induced retinopathy (OIR) model for retinopathy of prematurity (ROP). METHODS: In the OIR model, wild-type (WT) and alpha2-null mice were exposed to 75% oxygen for 5 days (postnatal day [P] 7 to P12) and subsequently returned to room air for 6 days (P12-P18). Retinas were collected at postnatal day 7, day 13, and day 18 and examined via hematoxylin and eosin and Lectin staining. Retinas were analyzed for retinal vascular area, neovascularization, VEGF expression, and Muller cell activation. Primary Muller cell cultures from WT and alpha2-null mice were isolated and analyzed for hypoxia-induced VEGF-A expression. RESULTS: In the retina, the alpha2beta1 integrin was minimally expressed in endothelial cells and strongly expressed in activated Muller cells. Isolated alpha2-null primary Muller cells demonstrated decreased hypoxia-induced VEGF-A expression. In the OIR model, alpha2-null mice displayed reduced hyperoxia-induced vaso-attenuation, reduced pathological retinal neovascularization, and decreased VEGF expression as compared to WT counterparts. CONCLUSIONS: Our data suggest that the alpha2beta1 integrin contributes to the pathogenesis of retinopathy. We describe a newly identified role for alpha2beta1 integrin in mediating hypoxia-induced Muller cell VEGF-A production. |
