Neurotrophins and neurotrophin receptors in proliferative diabetic retinopathy.

Neurotrophins (NTs) are emerging as important mediators of angiogenesis and fibrosis. We investigated the expression of the NTs nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) and their receptors TrkA, TrkB, and TrkC in proliferat...

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Autores principales:	Ahmed M Abu El-Asrar, Ghulam Mohammad, Gert De Hertogh, Mohd Imtiaz Nawaz, Kathleen Van Den Eynde, Mohammad Mairaj Siddiquei, Sofie Struyf, Ghislain Opdenakker, Karel Geboes
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4269333631c641ada1224aeebe9ee3c0
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spelling	oai:doaj.org-article:4269333631c641ada1224aeebe9ee3c02021-11-18T07:42:36ZNeurotrophins and neurotrophin receptors in proliferative diabetic retinopathy.1932-620310.1371/journal.pone.0065472https://doaj.org/article/4269333631c641ada1224aeebe9ee3c02013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23762379/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Neurotrophins (NTs) are emerging as important mediators of angiogenesis and fibrosis. We investigated the expression of the NTs nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) and their receptors TrkA, TrkB, and TrkC in proliferative diabetic retinopathy (PDR). As a comparison, we examined the expression of NTs and their receptors in the retinas of diabetic rats. Vitreous samples from 16 PDR and 15 nondiabetic patients were studied by Western blot analysis and enzyme-linked immunosorbent assay (ELISA). Epiretinal membranes from 17 patients with PDR were studied by immunohistochemistry. Rats were made diabetic with a single high dose of streptozotocin and retinas of rats were examined by Western blot analysis. Western blot analysis revealed a significant increase in the expression of NT-3 and NT-4 and the shedding of receptors TrkA and TrkB in vitreous samples from PDR patients compared to nondiabetic controls, whereas NGF and BDNF and the receptor TrkC were not detected with the use of Western blot analysis and ELISA. In epiretinal membranes, vascular endothelial cells and myofibroblasts expressed NT-3 and the receptors TrkA, TrkB and TrkC in situ, whereas NT-4 was not detected. The expression levels of NT-3 and NT-4 and the receptors TrkA and TrkB, both in intact and solubilized forms, were upregulated in the retinas of diabetic rats, whereas the receptor TrkC was not detected. Co-immunoprecipitation studies revealed binding between NT-3 and the receptors TrkA and TrkB in the retinas of diabetic rats. Our findings in diabetic eyes from humans and rats suggest that the increased expression levels within the NT-3 and NT-4/Trk axis are associated with the progression of PDR.Ahmed M Abu El-AsrarGhulam MohammadGert De HertoghMohd Imtiaz NawazKathleen Van Den EyndeMohammad Mairaj SiddiqueiSofie StruyfGhislain OpdenakkerKarel GeboesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e65472 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ahmed M Abu El-Asrar Ghulam Mohammad Gert De Hertogh Mohd Imtiaz Nawaz Kathleen Van Den Eynde Mohammad Mairaj Siddiquei Sofie Struyf Ghislain Opdenakker Karel Geboes Neurotrophins and neurotrophin receptors in proliferative diabetic retinopathy.
description	Neurotrophins (NTs) are emerging as important mediators of angiogenesis and fibrosis. We investigated the expression of the NTs nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) and their receptors TrkA, TrkB, and TrkC in proliferative diabetic retinopathy (PDR). As a comparison, we examined the expression of NTs and their receptors in the retinas of diabetic rats. Vitreous samples from 16 PDR and 15 nondiabetic patients were studied by Western blot analysis and enzyme-linked immunosorbent assay (ELISA). Epiretinal membranes from 17 patients with PDR were studied by immunohistochemistry. Rats were made diabetic with a single high dose of streptozotocin and retinas of rats were examined by Western blot analysis. Western blot analysis revealed a significant increase in the expression of NT-3 and NT-4 and the shedding of receptors TrkA and TrkB in vitreous samples from PDR patients compared to nondiabetic controls, whereas NGF and BDNF and the receptor TrkC were not detected with the use of Western blot analysis and ELISA. In epiretinal membranes, vascular endothelial cells and myofibroblasts expressed NT-3 and the receptors TrkA, TrkB and TrkC in situ, whereas NT-4 was not detected. The expression levels of NT-3 and NT-4 and the receptors TrkA and TrkB, both in intact and solubilized forms, were upregulated in the retinas of diabetic rats, whereas the receptor TrkC was not detected. Co-immunoprecipitation studies revealed binding between NT-3 and the receptors TrkA and TrkB in the retinas of diabetic rats. Our findings in diabetic eyes from humans and rats suggest that the increased expression levels within the NT-3 and NT-4/Trk axis are associated with the progression of PDR.
format	article
author	Ahmed M Abu El-Asrar Ghulam Mohammad Gert De Hertogh Mohd Imtiaz Nawaz Kathleen Van Den Eynde Mohammad Mairaj Siddiquei Sofie Struyf Ghislain Opdenakker Karel Geboes
author_facet	Ahmed M Abu El-Asrar Ghulam Mohammad Gert De Hertogh Mohd Imtiaz Nawaz Kathleen Van Den Eynde Mohammad Mairaj Siddiquei Sofie Struyf Ghislain Opdenakker Karel Geboes
author_sort	Ahmed M Abu El-Asrar
title	Neurotrophins and neurotrophin receptors in proliferative diabetic retinopathy.
title_short	Neurotrophins and neurotrophin receptors in proliferative diabetic retinopathy.
title_full	Neurotrophins and neurotrophin receptors in proliferative diabetic retinopathy.
title_fullStr	Neurotrophins and neurotrophin receptors in proliferative diabetic retinopathy.
title_full_unstemmed	Neurotrophins and neurotrophin receptors in proliferative diabetic retinopathy.
title_sort	neurotrophins and neurotrophin receptors in proliferative diabetic retinopathy.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/4269333631c641ada1224aeebe9ee3c0
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Neurotrophins and neurotrophin receptors in proliferative diabetic retinopathy.

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