p75NTR and Its Ligand ProNGF Activate Paracrine Mechanisms Etiological to the Vascular, Inflammatory, and Neurodegenerative Pathologies of Diabetic Retinopathy

Please use this identifier to cite or link to this item: http://hdl.handle.net/10045/57475
Información del item - Informació de l'item - Item information
Title: p75NTR and Its Ligand ProNGF Activate Paracrine Mechanisms Etiological to the Vascular, Inflammatory, and Neurodegenerative Pathologies of Diabetic Retinopathy
Authors: Barcelona, Pablo F. | Sitaras, Nicholas | Galan, Alba | Esquiva Sobrino, Gema | Jmaeff, Sean | Jian, Yifan | Sarunic, Marinko V. | Cuenca, Nicolás | Sapieha, Przemyslaw | Saragovi, H. Uri
Research Group/s: Neurobiología del Sistema Visual y Terapia de Enfermedades Neurodegenerativas (NEUROVIS)
Center, Department or Service: Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología
Keywords: Diabetes | Neurodegeneration | Neurotrophin | Pathophysiology | Receptor | Retina
Knowledge Area: Biología Celular
Issue Date: 24-Aug-2016
Publisher: Society for Neuroscience
Citation: The Journal of Neuroscience. 2016, 36(34): 8826-8841. doi:10.1523/JNEUROSCI.4278-15.2016
Abstract: In many diseases, expression and ligand-dependent activity of the p75NTR receptor can promote pericyte and vascular dysfunction, inflammation, glial activation, and neurodegeneration. Diabetic retinopathy (DR) is characterized by all of these pathological events. However, the mechanisms by which p75NTR may be implicated at each stage of DR pathology remain poorly understood. Using a streptozotocin mouse model of diabetic retinopathy, we report that p75NTR is upregulated very early in glia and in pericytes to mediate ligand-dependent induction of inflammatory cytokines, disruption of the neuro-glia-vascular unit, promotion of blood–retina barrier breakdown, edema, and neuronal death. In a mouse model of oxygen-induced retinopathy, mimicking proliferative DR, p75NTR-dependent inflammation leads to ischemia and pathological angiogenesis through Semaphorin 3A. The acute use of antagonists of p75NTR or antagonists of the ligand proNGF suppresses each distinct phase of pathology, ameliorate disease, and prevent disease progression. Thus, our study documents novel disease mechanisms and validates druggable targets for diabetic retinopathy.
Sponsor: This work was supported by the Canadian Institutes of Health Research and the Foundation to Fight Blindness to H.U.S. and the Canadian Diabetes Association to P.S.
URI: http://hdl.handle.net/10045/57475
ISSN: 0270-6474 (Print) | 1529-2401 (Online)
DOI: 10.1523/JNEUROSCI.4278-15.2016
Language: eng
Type: info:eu-repo/semantics/article
Rights: © 2016 the authors
Peer Review: si
Publisher version: http://dx.doi.org/10.1523/JNEUROSCI.4278-15.2016
Appears in Collections:INV - NEUROVIS - Artículos de Revistas

Files in This Item:
Files in This Item:
File Description SizeFormat 
Thumbnail2016_Barcelona_etal_JNeurosci.pdf6,22 MBAdobe PDFOpen Preview


Items in RUA are protected by copyright, with all rights reserved, unless otherwise indicated.