期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 288, 期 24, 页码 17631-17642出版社
ELSEVIER
DOI: 10.1074/jbc.M113.468819
关键词
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资金
- Instituto de Salud Carlos III [PI 061417]
- Plan Nacional I + D + I Grant [SAF2011-24698]
- Generalitat de Catalunya, Spain [2009 SGR224]
- European Community [CLINIGENE LSHB-CT-2006-018933]
- Fundacion Ramon Areces
- Ministerio de Educacion y Ciencia
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.
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