Insulin-like growth factor I (IGF-I)-induced chronic gliosis and retinal stress lead to neurodegeneration in a mouse model of retinopathy
Villacampa Alcubierre, Pilar (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Bosch i Tubert, Fàtima (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Ribera Sánchez, Albert (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Motas, Sandra (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Ramírez, Laura (Universidad de Alcalá. Departamento de Fisiología)
Garcia, Miquel (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
de la Villa, Pedro (Universidad de Alcalá. Departamento de Fisiología)
Haurigot Mendonça, Virginia (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Data:	2013
Resum:	Insulin-like growth factor I (IGF-I) exerts multiple effects on different retinal cell types in both physiological and pathological conditions. Despite the growth factor's extensively described neuroprotective actions, transgenic mice with increased intraocular levels of IGF-I showed progressive impairment of electroretinographic amplitudes up to complete loss of response, with loss of photoreceptors and bipolar, ganglion, and amacrine neurons. Neurodegeneration was preceded by the overexpression of genes related to retinal stress, acute-phase response, and gliosis, suggesting that IGF-I altered normal retinal homeostasis. Indeed, gliosis and microgliosis were present from an early age in transgenic mice, before other alterations occurred, and were accompanied by signs of oxidative stress and impaired glutamate recycling. Older mice also showed overproduction of pro-inflammatory cytokines. Our results suggest that, when chronically increased, intraocular IGF-I is responsible for the induction of deleterious cellular processes that can lead to neurodegeneration, and they highlight the importance that this growth factor may have in the pathogenesis of conditions such as ischemic or diabetic retinopathy.
Ajuts:	Ministerio de Economía y Competitividad SAF2011-24698 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-224
Nota:	Altres ajuts: CLINIGENE/LSHB-CT-2006-018933
Drets:	Tots els drets reservats.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Animal Models ; Glia ; Insulin-like Growth Factor (IGF) ; Neurodegeneration ; Retina
Publicat a:	Journal of biological chemistry, Vol. 288 Núm. 24 (Juny 2013) , p. 17631-17642, ISSN 1083-351X

DOI: 10.1074/jbc.M113.468819
PMID: 23620587

13 p, 2.9 MB

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