April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Effect Of IGF-1/IGF-1R System On Glial Müller Cells
Author Affiliations & Notes
  • Maria C. Sanchez
    CIBICI-Dpto de Bioquimica Clinica, Fac de Ciencias Quimicas UNC, Cordoba, Argentina
  • Valeria E. Lorenc
    CIBICI-Dpto de Bioquimica Clinica, Fac de Ciencias Quimicas UNC, Cordoba, Argentina
  • Pablo F. Barcelona
    CIBICI-Dpto de Bioquimica Clinica, Fac de Ciencias Quimicas UNC, Cordoba, Argentina
  • Susana G. Ortiz
    CIBICI-Dpto de Bioquimica Clinica, Fac de Ciencias Quimicas UNC, Cordoba, Argentina
  • Footnotes
    Commercial Relationships  Maria C. Sanchez, None; Valeria E. Lorenc, None; Pablo F. Barcelona, None; Susana G. Ortiz, None
  • Footnotes
    Support  SECyT-UNC, CONICET, FONCyT
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 4848. doi:
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      Maria C. Sanchez, Valeria E. Lorenc, Pablo F. Barcelona, Susana G. Ortiz; Effect Of IGF-1/IGF-1R System On Glial Müller Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4848.

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Abstract

Purpose: : During the normal vascular development of the retina as well as in the pathogenesis of retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR) the involvement of IGF-1 and its receptor (IGF-1R) are required. Müller cells (MC) are known to be implicated in these diseases by producing Vascular Endothelial Growth Factor (VEGF) and secreting metaloproteinases (MMPs) that participate in the extracellular proteolysis during neovascularization. However, at present, it is not well known the function of IGF-1/IGF-1R system during this process. We have previously demonstrated the IGF-1 induction on the migratory capacity of MC, in a process that may be mediated by MMP-2. In this work we evaluate the effect of IGF-1 on the IGF-1R activation and the relationship to the migration process on different matrix-protein-coated surfaces.

Methods: : The human MIO-M1 cell line was used and cultured in presence of 10 nM IGF-1 for different times (1, 4 and 8 h). The IGF-1R and pIGF-1R expression was analyzed by both Western blot (WB) and inmunoflourescence analysis. To demonstrate the specifity of the IGF-1 activation, cells were pre-incubated with anti IGF-1R antibody (αIR3) and the induced signalling pathways were evaluated by WB. Cell migration was determined by wound-healing assay on collagen or laminin-coated surface using time-lapse video microscopy.

Results: : By WB we observed that, under IGF-1 stimulus, IGF-1R increased its phosphorilation in MC extracts, but not its own expression. IGF-1 also produced MAPK-ERK1/2 and PI3K/Akt activation, but these pathways were inhibited by anti IGF-1R antibody, indicating that these transduction events were specific of the IGF-1 binding to its receptor. Finally, this activation may be involved in the migration process due to the pre incubation of the bloquing antibody reduced the cell motility.

Conclusions: : The present study demonstrates that IGF-1 regulates the IGF-1R activation in MC, which would mediate the migration process in these cells.

Keywords: Muller cells • neovascularization • growth factors/growth factor receptors 
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