| First Author | Du W | Year | 2012 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 53 |
| Issue | 4 | Pages | 1990-8 |
| PubMed ID | 22408005 | Mgi Jnum | J:327843 |
| Mgi Id | MGI:6840327 | Doi | 10.1167/iovs.11-8788 |
| Citation | Du W, et al. (2012) Ephrin-a4 is involved in retinal neovascularization by regulating the VEGF signaling pathway. Invest Ophthalmol Vis Sci 53(4):1990-8 |
| abstractText | PURPOSE: Retinal neovascularization (NV) is a major cause of blindness. Recent research suggests that factors other than VEGF participate in this process. This study aimed to determine the role of ephrin-A4 in retinal NV. METHODS: The expression and effect of ephrin-A4 was investigated in a mouse model of oxygen-induced retinopathy (OIR) and the RF/6A retina endothelial cell line. Ephrin-A4 expression and VEGF signaling pathway phosphorylation were determined by PCR, immunohistochemistry, and western blot analyses. ShRNA was used to silence ephrin-A4 in vitro and in vivo. Retinal flat mounts and tube formation assays were performed to evaluate ephrin-A4 function in the NV process in vivo and in vitro. RESULTS: Ephrin-A4 was overexpressed in the retina of OIR mice and in RF/6A and RPE cells after CoCl(2) stimulation. In vitro, Ephrin-A4/Fc treatment significantly increased the tube number of RF/6A cells on a membrane preparation and the phosphorylation levels of VEGR2, Akt1, and ERK1/2 in RF/6A cells. Moreover, ephrin-A4 knockout markedly suppressed pathologic neovascularization in vivo and inhibited the proliferation and tube formation capacity of RF/6A cells in vitro. Furthermore, in the absence of ephrin-A4, the phosphorylation of VEGFR2, Akt1, and ERK1/2 was defective under VEGF(1)(6)(5) stimulation, and the proangiogenic function of VEGF(1)(6)(5) was also compromised. CONCLUSIONS: This study suggests that ephrin-A4 plays an important role in retinal NV and is a potential target against retinal NV. The proangiogenic function of ephrin-A4 may be linked to its crucial role in the VEGF signaling pathway. |
