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Dysfunctional cGMP Signaling Leads to Age-Related Retinal Vascular Alterations and Astrocyte Remodeling in Mice
The nitric oxide–guanylyl cyclase-1–cyclic guanylate monophosphate (NO–GC-1–cGMP) pathway is integral to the control of vascular tone and morphology. Mice lacking the alpha catalytic domain of guanylate cyclase (GC1(−/−)) develop retinal ganglion cell (RGC) degeneration with age, with only modest fl...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954518/ https://www.ncbi.nlm.nih.gov/pubmed/35328488 http://dx.doi.org/10.3390/ijms23063066 |
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author | Holden, Joseph M. Al Hussein Al Awamlh, Sara Croteau, Louis-Philippe Boal, Andrew M. Rex, Tonia S. Risner, Michael L. Calkins, David J. Wareham, Lauren K. |
author_facet | Holden, Joseph M. Al Hussein Al Awamlh, Sara Croteau, Louis-Philippe Boal, Andrew M. Rex, Tonia S. Risner, Michael L. Calkins, David J. Wareham, Lauren K. |
author_sort | Holden, Joseph M. |
collection | PubMed |
description | The nitric oxide–guanylyl cyclase-1–cyclic guanylate monophosphate (NO–GC-1–cGMP) pathway is integral to the control of vascular tone and morphology. Mice lacking the alpha catalytic domain of guanylate cyclase (GC1(−/−)) develop retinal ganglion cell (RGC) degeneration with age, with only modest fluctuations in intraocular pressure (IOP). Increasing the bioavailability of cGMP in GC1(−/−) mice prevents neurodegeneration independently of IOP, suggesting alternative mechanisms of retinal neurodegeneration. In continuation to these studies, we explored the hypothesis that dysfunctional cGMP signaling leads to changes in the neurovascular unit that may contribute to RGC degeneration. We assessed retinal vasculature and astrocyte morphology in young and aged GC1(−/−) and wild type mice. GC1(−/−) mice exhibit increased peripheral retinal vessel dilation and shorter retinal vessel branching with increasing age compared to Wt mice. Astrocyte cell morphology is aberrant, and glial fibrillary acidic protein (GFAP) density is increased in young and aged GC1(−/−) mice, with areas of dense astrocyte matting around blood vessels. Our results suggest that proper cGMP signaling is essential to retinal vessel morphology with increasing age. Vascular changed are preceded by alterations in astrocyte morphology which may together contribute to retinal neurodegeneration and loss of visual acuity observed in GC1(−/−) mice. |
format | Online Article Text |
id | pubmed-8954518 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89545182022-03-26 Dysfunctional cGMP Signaling Leads to Age-Related Retinal Vascular Alterations and Astrocyte Remodeling in Mice Holden, Joseph M. Al Hussein Al Awamlh, Sara Croteau, Louis-Philippe Boal, Andrew M. Rex, Tonia S. Risner, Michael L. Calkins, David J. Wareham, Lauren K. Int J Mol Sci Article The nitric oxide–guanylyl cyclase-1–cyclic guanylate monophosphate (NO–GC-1–cGMP) pathway is integral to the control of vascular tone and morphology. Mice lacking the alpha catalytic domain of guanylate cyclase (GC1(−/−)) develop retinal ganglion cell (RGC) degeneration with age, with only modest fluctuations in intraocular pressure (IOP). Increasing the bioavailability of cGMP in GC1(−/−) mice prevents neurodegeneration independently of IOP, suggesting alternative mechanisms of retinal neurodegeneration. In continuation to these studies, we explored the hypothesis that dysfunctional cGMP signaling leads to changes in the neurovascular unit that may contribute to RGC degeneration. We assessed retinal vasculature and astrocyte morphology in young and aged GC1(−/−) and wild type mice. GC1(−/−) mice exhibit increased peripheral retinal vessel dilation and shorter retinal vessel branching with increasing age compared to Wt mice. Astrocyte cell morphology is aberrant, and glial fibrillary acidic protein (GFAP) density is increased in young and aged GC1(−/−) mice, with areas of dense astrocyte matting around blood vessels. Our results suggest that proper cGMP signaling is essential to retinal vessel morphology with increasing age. Vascular changed are preceded by alterations in astrocyte morphology which may together contribute to retinal neurodegeneration and loss of visual acuity observed in GC1(−/−) mice. MDPI 2022-03-12 /pmc/articles/PMC8954518/ /pubmed/35328488 http://dx.doi.org/10.3390/ijms23063066 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Holden, Joseph M. Al Hussein Al Awamlh, Sara Croteau, Louis-Philippe Boal, Andrew M. Rex, Tonia S. Risner, Michael L. Calkins, David J. Wareham, Lauren K. Dysfunctional cGMP Signaling Leads to Age-Related Retinal Vascular Alterations and Astrocyte Remodeling in Mice |
title | Dysfunctional cGMP Signaling Leads to Age-Related Retinal Vascular Alterations and Astrocyte Remodeling in Mice |
title_full | Dysfunctional cGMP Signaling Leads to Age-Related Retinal Vascular Alterations and Astrocyte Remodeling in Mice |
title_fullStr | Dysfunctional cGMP Signaling Leads to Age-Related Retinal Vascular Alterations and Astrocyte Remodeling in Mice |
title_full_unstemmed | Dysfunctional cGMP Signaling Leads to Age-Related Retinal Vascular Alterations and Astrocyte Remodeling in Mice |
title_short | Dysfunctional cGMP Signaling Leads to Age-Related Retinal Vascular Alterations and Astrocyte Remodeling in Mice |
title_sort | dysfunctional cgmp signaling leads to age-related retinal vascular alterations and astrocyte remodeling in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954518/ https://www.ncbi.nlm.nih.gov/pubmed/35328488 http://dx.doi.org/10.3390/ijms23063066 |
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