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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254968.pdf | 3.83 MB | Adobe PDF | View/Open |
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