Purchase this article with an account.
C. Shao, S.X. Zhang, J. Fant, Y. Chen, B. Rohrer, J. Ma; Angiogenic Inhibitor Plasminogen Kringle 5 Down-Regulates the Expression of Vascular Endothelial Growth Factor in Müller Cells . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2879.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Vascular endothelial growth factor (VEGF) plays an important role in retinal neovascularization. Müller cells are a major source of VEGF in the retina. Plasminogen kringle 5 (K5) is known to inhibit retinal neovascularization. This study was designed to determine if K5 regulates VEGF in Müller cells. Methods: A rat Müller cell line (rMC-1) was treated with cobalt chloride (CoCl2 200 µM) to induce VEGF expression and K5 was administered at different concentrations (50, 100, 200, 400 nM) in a serum-free medium. Western blot analysis was used to measure intracellular VEGF levels, and ELISA was used to measure secreted VEGF in the medium. The intracellular VEGF level was normalized by ß-actin and the secreted VEGF level by the total protein concentration. To determine the in vivo effect, rats with oxygen-induced retinopathy (OIR) received intravitreal injections of K5 with different doses (0.3, 1, 3, 10 µg/eye). Immunohistochemistry was performed to determine the expression of VEGF in the retinal Müller cells. Results: In the Müller cell line, CoCl2 significantly increased VEGF levels both in the cells and in the medium. Western blot analysis and ELISA both showed that the expression of VEGF induced by CoCl2 was inhibited by K5 in a concentration-dependent manner. In OIR rats, immunohistochemistry showed that K5 decreased the expression of VEGF in Müller cells. This in vivo effect also appeared to be K5 dose-dependent. Conclusions: These results indicate that K5 decreases the VEGF expression induced by CoCl2 in a Müller cell line and in retinal Müller cells of OIR rats. The K5-induced down-regulation of VEGF in Müller cells may be responsible for its anti-angiogenic activity.
This PDF is available to Subscribers Only