Inhibition of reactive gliosis prevents neovascular growth in the mouse model of oxygen-induced retinopathy.

Retinal neovascularization (NV) is a major cause of blindness in ischemic retinopathies. Previous investigations have indicated that ischemia upregulates GFAP and PDGF-B expression. GFAP overexpression is a hallmark of reactive gliosis (RG), which is the major pathophysiological feature of retinal d...

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Autores principales: Michael DeNiro, Falah H Al-Mohanna, Futwan A Al-Mohanna
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Publicado: Public Library of Science (PLoS) 2011
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spelling oai:doaj.org-article:347042e9462c47fbaebdee227e3cd8352021-11-18T06:50:14ZInhibition of reactive gliosis prevents neovascular growth in the mouse model of oxygen-induced retinopathy.1932-620310.1371/journal.pone.0022244https://doaj.org/article/347042e9462c47fbaebdee227e3cd8352011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21779402/?tool=EBIhttps://doaj.org/toc/1932-6203Retinal neovascularization (NV) is a major cause of blindness in ischemic retinopathies. Previous investigations have indicated that ischemia upregulates GFAP and PDGF-B expression. GFAP overexpression is a hallmark of reactive gliosis (RG), which is the major pathophysiological feature of retinal damage. In addition, PDGF-B has been implicated in proliferative retinopathies. It was the aim of this study to gain insights on the possible pharmacological interventions to modulate PDGF-B and GFAP expression, and its influence on RG and NV. We used an array of assays to evaluate the effects of YC-1, a small molecule inhibitor of HIF-1 and a novel NO-independent activator of soluble guanylyl cyclase (sGC), on RG and NV, in vivo and in vitro. When compared to the DMSO-treated retinas, dual-intravitreal injections of YC-1, in vivo: (1) suppressed the development and elongation of neovascular sprouts in the retinas of the oxygen-induced retinopathy (OIR) mouse model; and (2) reduced ischemia-induced overexpression of GFAP and PDGF-B at the message (by 64.14±0.5% and 70.27±0.04%) and the protein levels (by 65.52±0.02% and 57.59±0.01%), respectively. In addition, at 100 µM, YC-1 treatment downregulated the hypoxia-induced overexpression of GFAP and PDGF-B at the message level in rMC-1 cells (by 71.42±0.02% and 75±0.03%), and R28 cells (by 58.62±0.02% and 50.00±0.02%), respectively; whereas, the protein levels of GFAP and PDGF-B were reduced (by 78.57±0.02% and 77.55±0.01%) in rMC-1 cells, and (by 81.44±0.02% and 79.16±0.01%) in R28 cells, respectively. We demonstrate that YC-1 reversed RG during ischemic retinopathy via impairing the expression of GFAP and PDGF-B in glial cells. This is the first investigation that delves into the reversal of RG during ischemic retinal vasculopathies. In addition, the study reveals that YC-1 may exert promising therapeutic effects in the treatment of retinal and neuronal pathologies.Michael DeNiroFalah H Al-MohannaFutwan A Al-MohannaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 7, p e22244 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Michael DeNiro
Falah H Al-Mohanna
Futwan A Al-Mohanna
Inhibition of reactive gliosis prevents neovascular growth in the mouse model of oxygen-induced retinopathy.
description Retinal neovascularization (NV) is a major cause of blindness in ischemic retinopathies. Previous investigations have indicated that ischemia upregulates GFAP and PDGF-B expression. GFAP overexpression is a hallmark of reactive gliosis (RG), which is the major pathophysiological feature of retinal damage. In addition, PDGF-B has been implicated in proliferative retinopathies. It was the aim of this study to gain insights on the possible pharmacological interventions to modulate PDGF-B and GFAP expression, and its influence on RG and NV. We used an array of assays to evaluate the effects of YC-1, a small molecule inhibitor of HIF-1 and a novel NO-independent activator of soluble guanylyl cyclase (sGC), on RG and NV, in vivo and in vitro. When compared to the DMSO-treated retinas, dual-intravitreal injections of YC-1, in vivo: (1) suppressed the development and elongation of neovascular sprouts in the retinas of the oxygen-induced retinopathy (OIR) mouse model; and (2) reduced ischemia-induced overexpression of GFAP and PDGF-B at the message (by 64.14±0.5% and 70.27±0.04%) and the protein levels (by 65.52±0.02% and 57.59±0.01%), respectively. In addition, at 100 µM, YC-1 treatment downregulated the hypoxia-induced overexpression of GFAP and PDGF-B at the message level in rMC-1 cells (by 71.42±0.02% and 75±0.03%), and R28 cells (by 58.62±0.02% and 50.00±0.02%), respectively; whereas, the protein levels of GFAP and PDGF-B were reduced (by 78.57±0.02% and 77.55±0.01%) in rMC-1 cells, and (by 81.44±0.02% and 79.16±0.01%) in R28 cells, respectively. We demonstrate that YC-1 reversed RG during ischemic retinopathy via impairing the expression of GFAP and PDGF-B in glial cells. This is the first investigation that delves into the reversal of RG during ischemic retinal vasculopathies. In addition, the study reveals that YC-1 may exert promising therapeutic effects in the treatment of retinal and neuronal pathologies.
format article
author Michael DeNiro
Falah H Al-Mohanna
Futwan A Al-Mohanna
author_facet Michael DeNiro
Falah H Al-Mohanna
Futwan A Al-Mohanna
author_sort Michael DeNiro
title Inhibition of reactive gliosis prevents neovascular growth in the mouse model of oxygen-induced retinopathy.
title_short Inhibition of reactive gliosis prevents neovascular growth in the mouse model of oxygen-induced retinopathy.
title_full Inhibition of reactive gliosis prevents neovascular growth in the mouse model of oxygen-induced retinopathy.
title_fullStr Inhibition of reactive gliosis prevents neovascular growth in the mouse model of oxygen-induced retinopathy.
title_full_unstemmed Inhibition of reactive gliosis prevents neovascular growth in the mouse model of oxygen-induced retinopathy.
title_sort inhibition of reactive gliosis prevents neovascular growth in the mouse model of oxygen-induced retinopathy.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/347042e9462c47fbaebdee227e3cd835
work_keys_str_mv AT michaeldeniro inhibitionofreactivegliosispreventsneovasculargrowthinthemousemodelofoxygeninducedretinopathy
AT falahhalmohanna inhibitionofreactivegliosispreventsneovasculargrowthinthemousemodelofoxygeninducedretinopathy
AT futwanaalmohanna inhibitionofreactivegliosispreventsneovasculargrowthinthemousemodelofoxygeninducedretinopathy
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