Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/223478
Title: Increased intraocular insulin-like growth factor-I triggers blood-retinal barrier breakdown
Author: 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
Keywords: Electroforesi
Bestiar boví
Retina
Persones grans
Electrophoresis
Cattle
Retina
Older people
Issue Date: 21-Aug-2009
Publisher: American Society for Biochemistry and Molecular Biology
Abstract: 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.
Note: Reproducció del document publicat a: https://doi.org/10.1074/jbc.M109.014787
It is part of: Journal of Biological Chemistry, 2009, vol. 284, num.34, p. 22961-22969
URI: https://hdl.handle.net/2445/223478
Related resource: https://doi.org/10.1074/jbc.M109.014787
ISSN: 0021-9258
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)

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