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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/223478
Increased intraocular insulin-like growth factor-I triggers blood-retinal barrier breakdown
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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 and tissue damage resulting in visual impairment. Insulin-like growth factor-I (IGF-I) is involved in these processes, although the relative contribution of increased systemic versus intraocular IGF-I remains controversial. Here, to elucidate the role of this factor in BRB breakdown, transgenic mice with either local or systemic elevations of IGF-I have been examined. High intraocular IGF-I, resulting from overexpression of IGF-I in the retina, increased IGF-I receptor content and signaling and led to accumulation of vascular endothelial growth factor. This was parallel to up-regulation of vascular Intercellular adhesion molecule I and retinal infiltration by bone marrow-derived microglial cells. These alterations resulted in increased vessel paracellular permeability to both low and high molecular weight compounds in IGF-I-overexpressing retinas and agreed with the loss of vascular tight junction integrity observed by electron microscopy and the altered junctional protein content. In contrast, mice with chronically elevated serum IGF-I did not show alterations in the retinal vasculature structure and permeability, indicating that circulating IGF-I cannot initiate BRB breakdown. Consistent with a key role of IGF-I signaling in retinal diseases, a strong up-regulation of the IGF-I receptor in human retinas with marked gliosis was also observed. Thus, this study demonstrates that intraocular IGF-I, but not systemic IGF-I, is sufficient to trigger processes leading to BRB breakdown and increased retinal vascular permeability. Therefore, therapeutic interventions designed to counteract local IGF-I effects may prove successful to prevent BRB disruption.
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HAURIGOT, Virginia, VILLACAMPA, Pilar, RIBERA, Albert, LLOMBART, Cristina, BOSCH, Assumpció, NACHER, Victor, RAMOS, David, AYUSO, Eduard, SEGOVIA, José c., BUEREN, Juan a., RUBERTE PARÍS, Jesús, BOSCH I TUBERT, Fàtima. Increased intraocular insulin-like growth factor-I triggers blood-retinal barrier breakdown. _Journal of Biological Chemistry_. 2009. Vol. 284, núm. 34, pàgs. 22961-22969. [consulta: 28 de novembre de 2025]. ISSN: 0021-9258. [Disponible a: https://hdl.handle.net/2445/223478]