Glial M¨¹ller cells (MC) are involved in retinal neovascularization, but very little is known of the contribution of these cells to this process. Hypoxia and growth factors are postulated to be involved in the development of retinal neovascularization through the regulation of extracellular proteinase production. However, the factors and mechanisms that regulate the expression of these enzymes are not well characterized. Previously we demonstrated that matrix metalloproteinases (MMPs) are elevated in the retina during the neovascularization process. Herein we investigated the a2-M effect on intracellular signaling pathways in primary cultures of MC that express LRP-1, evaluating the potential role of these transduction pathways as a regulator of MMPs.
MC were isolated from C57BL/6 mice and the LRP-1 expression was detected by Western blotting and immunocytochemistry. MAPK-ERK1/2 and PKB pathways were analyzed by Western blotting in MC cultured in presence of a2-M. The role of ¦Á2-M in stimulating retinal glial cell proteinase production was evaluated by zymographic analysis.
We showed that nearly 95-100% of MC expressed LRP-
a2-M increased the MMP-2 gelatinolytic activity after 24 hours of stimulation.