Integrins in human Retinal Pigmented Epithelial (RPE) cells: Role of extracellular matrix proteins (ECMs) and hypoxia on the secretion of growth factors

The present study was undertaken to define the role of integrins, ECMs and hypoxia on the regulation of RPE integrin-mediated adhesion and growth factor secretory functions. A differential and high expression of levels of αvβ5 followed by α5β1 and αvβ3 integrins are shown in human RPE using FACS analysis with specific monoclonal antibodies for these different integrins. Additionally, adhesion of RPE to extracellular matrix (ECM) proteins is shown to be mediated to great extent via αvβ5 and to a lesser extent via α5β1 and αvβ3. The role of ECM proteins on RPE secretion of growth factors including bFGF and VEGF showed soluble thrombospondin to be the most effective ECM. Additionally, the effects of hypoxic versus normoxic conditions on RPE secretion of growth factors demonstrated a time-dependent 2-3 fold increase in the up-regulation of VEGF but not bFGF secretion. These data suggest a potential role of αvβ5 in RPE adhesion to ECM and that ECM and hypoxia play a key role in the regulation of RPE growth functions.