%0 Journal Article
%T ¦Â1 Integrin-Focal Adhesion Kinase (FAK) Signaling Modulates Retinal Ganglion Cell (RGC) Survival
%A Andrea Rachelle C. Santos
%A Raul G. Corredor
%A Betty Albo Obeso
%A Ephraim F. Trakhtenberg
%A Ying Wang
%A Jamie Ponmattam
%A Galina Dvoriantchikova
%A Dmitry Ivanov
%A Valery I. Shestopalov
%A Jeffrey L. Goldberg
%A Mary Elizabeth Fini
%A Michaela Livia Bajenaru
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0048332
%X Extracellular matrix (ECM) integrity in the central nervous system (CNS) is essential for neuronal homeostasis. Signals from the ECM are transmitted to neurons through integrins, a family of cell surface receptors that mediate cell attachment to ECM. We have previously established a causal link between the activation of the matrix metalloproteinase-9 (MMP-9), degradation of laminin in the ECM of retinal ganglion cells (RGCs), and RGC death in a mouse model of retinal ischemia-reperfusion injury (RIRI). Here we investigated the role of laminin-integrin signaling in RGC survival in vitro, and after ischemia in vivo. In purified primary rat RGCs, stimulation of the ¦Â1 integrin receptor with laminin, or agonist antibodies enhanced RGC survival in correlation with activation of ¦Â1 integrin¡¯s major downstream regulator, focal adhesion kinase (FAK). Furthermore, ¦Â1 integrin binding and FAK activation were required for RGCs¡¯ survival response to laminin. Finally, in vivo after RIRI, we observed an up-regulation of MMP-9, proteolytic degradation of laminin, decreased RGC expression of ¦Â1 integrin, FAK and Akt dephosphorylation, and reduced expression of the pro-survival molecule bcl-xL in the period preceding RGC apoptosis. RGC death was prevented, in the context of laminin degradation, by maintaining ¦Â1 integrin activation with agonist antibodies. Thus, disruption of homeostatic RGC-laminin interaction and signaling leads to cell death after retinal ischemia, and maintaining integrin activation may be a therapeutic approach to neuroprotection.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0048332