Increased Intraocular Insulin-like Growth Factor-I Triggers Blood-Retinal Barrier Breakdown

• DOI: 10.1074/jbc.m109.014787
• Publication Date: 2009-05-28T00:22:57Z
• Authors: Virginia Haurigot; Pilar Villacampa; Albert Ribera; Cristina Llombart; Assumpcio Bosch; Victor Nacher; David Ramos; Eduard Ayuso; José C. Segovia; Juan A. Bueren; Jesus Ruberte; Fatima Bosch
• Keywords: Vascular permeability; Blood–retinal barrier

Blood-retinal barrier (BRB) breakdown is a key event in diabetic retinopathy and other ocular disorders that leads to increased retinal vascular permeability. This causes edema tissue damage resulting visual impairment. Insulin-like growth factor-I (IGF-I) involved these processes, although the relative contribution of systemic versus intraocular IGF-I remains controversial. Here, elucidate role this factor BRB breakdown, transgenic mice with either local or elevations have been examined. High IGF-I, from overexpression retina, receptor content signaling led accumulation endothelial factor. was parallel up-regulation Intercellular adhesion molecule I infiltration by bone marrow-derived microglial cells. These alterations resulted vessel paracellular permeability both low high molecular weight compounds IGF-I-overexpressing retinas agreed loss tight junction integrity observed electron microscopy altered junctional protein content. In contrast, chronically elevated serum did not show vasculature structure permeability, indicating circulating cannot initiate breakdown. Consistent diseases, strong human marked gliosis also observed. Thus, study demonstrates but sufficient trigger processes leading Therefore, therapeutic interventions designed counteract effects may prove successful prevent disruption.