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The Nicotinic Cholinergic Pathway Contributes to Retinal Neovascularization in a Mouse Model of Retinopathy of Prematurity

PURPOSE: To investigate the role of nicotinic acetylcholine receptors (nAChRs) in retinal vascular development and ischemia-induced retinal neovascularization (NV). METHODS: The expression of nAChR subtypes and VEGF signaling pathway components was assessed in mice with and without oxygen-induced is...

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Autores principales: Hackett, Sean F., Seidel, Christopher, Abraham, Sheena, Chadha, Rishi, Fortmann, Seth D., Campochiaro, Peter A., Cooke, John P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020715/
https://www.ncbi.nlm.nih.gov/pubmed/28241318
http://dx.doi.org/10.1167/iovs.16-20670
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author Hackett, Sean F.
Seidel, Christopher
Abraham, Sheena
Chadha, Rishi
Fortmann, Seth D.
Campochiaro, Peter A.
Cooke, John P.
author_facet Hackett, Sean F.
Seidel, Christopher
Abraham, Sheena
Chadha, Rishi
Fortmann, Seth D.
Campochiaro, Peter A.
Cooke, John P.
author_sort Hackett, Sean F.
collection PubMed
description PURPOSE: To investigate the role of nicotinic acetylcholine receptors (nAChRs) in retinal vascular development and ischemia-induced retinal neovascularization (NV). METHODS: The expression of nAChR subtypes and VEGF signaling pathway components was assessed in mice with and without oxygen-induced ischemic retinopathy by comparing expression levels at postnatal day (P) 14 and P17 in mice exposed to 75% oxygen from P7 to P12 and returned to room air versus mice pups that were exposed to ambient oxygen levels during the same period. The effect of topical or intraocular injection of mecamylamine, a nonspecific nAChR antagonist, or targeted deletion of α7- or α9-nAChRs on ischemia-induced retinal NV was determined by comparing the amount of retinal NV at P17 in these mice versus appropriate controls. RESULTS: The expression of nAChR subunits and components of the VEGF signaling pathways was increased in ischemic retina. Topical application or intraocular injection of mecamylamine decreased retinal NV in this model. Mecamylamine had no effect on normal retinal vascular development or on revascularization of the central retinal area of nonperfusion in mice with ischemic retinopathy. Targeted deletion of α9, but not α7, nAChR receptor subunits reduced retinal NV in mice with ischemic retinopathy. CONCLUSION: These data suggest that nAChR signaling, primarily through the α9 nAChR subunit, contributes to ischemia-induced retinal NV, but not retinal vascular development. Mecamylamine or a specific α9 nAChR antagonist could be considered for treatment of retinopathy of prematurity and other ischemic retinopathies.
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spelling pubmed-60207152018-06-29 The Nicotinic Cholinergic Pathway Contributes to Retinal Neovascularization in a Mouse Model of Retinopathy of Prematurity Hackett, Sean F. Seidel, Christopher Abraham, Sheena Chadha, Rishi Fortmann, Seth D. Campochiaro, Peter A. Cooke, John P. Invest Ophthalmol Vis Sci Retinal Cell Biology PURPOSE: To investigate the role of nicotinic acetylcholine receptors (nAChRs) in retinal vascular development and ischemia-induced retinal neovascularization (NV). METHODS: The expression of nAChR subtypes and VEGF signaling pathway components was assessed in mice with and without oxygen-induced ischemic retinopathy by comparing expression levels at postnatal day (P) 14 and P17 in mice exposed to 75% oxygen from P7 to P12 and returned to room air versus mice pups that were exposed to ambient oxygen levels during the same period. The effect of topical or intraocular injection of mecamylamine, a nonspecific nAChR antagonist, or targeted deletion of α7- or α9-nAChRs on ischemia-induced retinal NV was determined by comparing the amount of retinal NV at P17 in these mice versus appropriate controls. RESULTS: The expression of nAChR subunits and components of the VEGF signaling pathways was increased in ischemic retina. Topical application or intraocular injection of mecamylamine decreased retinal NV in this model. Mecamylamine had no effect on normal retinal vascular development or on revascularization of the central retinal area of nonperfusion in mice with ischemic retinopathy. Targeted deletion of α9, but not α7, nAChR receptor subunits reduced retinal NV in mice with ischemic retinopathy. CONCLUSION: These data suggest that nAChR signaling, primarily through the α9 nAChR subunit, contributes to ischemia-induced retinal NV, but not retinal vascular development. Mecamylamine or a specific α9 nAChR antagonist could be considered for treatment of retinopathy of prematurity and other ischemic retinopathies. The Association for Research in Vision and Ophthalmology 2017-02 /pmc/articles/PMC6020715/ /pubmed/28241318 http://dx.doi.org/10.1167/iovs.16-20670 Text en Copyright 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Retinal Cell Biology
Hackett, Sean F.
Seidel, Christopher
Abraham, Sheena
Chadha, Rishi
Fortmann, Seth D.
Campochiaro, Peter A.
Cooke, John P.
The Nicotinic Cholinergic Pathway Contributes to Retinal Neovascularization in a Mouse Model of Retinopathy of Prematurity
title The Nicotinic Cholinergic Pathway Contributes to Retinal Neovascularization in a Mouse Model of Retinopathy of Prematurity
title_full The Nicotinic Cholinergic Pathway Contributes to Retinal Neovascularization in a Mouse Model of Retinopathy of Prematurity
title_fullStr The Nicotinic Cholinergic Pathway Contributes to Retinal Neovascularization in a Mouse Model of Retinopathy of Prematurity
title_full_unstemmed The Nicotinic Cholinergic Pathway Contributes to Retinal Neovascularization in a Mouse Model of Retinopathy of Prematurity
title_short The Nicotinic Cholinergic Pathway Contributes to Retinal Neovascularization in a Mouse Model of Retinopathy of Prematurity
title_sort nicotinic cholinergic pathway contributes to retinal neovascularization in a mouse model of retinopathy of prematurity
topic Retinal Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020715/
https://www.ncbi.nlm.nih.gov/pubmed/28241318
http://dx.doi.org/10.1167/iovs.16-20670
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