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Retinal Pigment Epithelium Remodeling in Mouse Models of Retinitis Pigmentosa
In retinitis pigmentosa (RP), one of many possible genetic mutations causes rod degeneration, followed by cone secondary death leading to blindness. Accumulating evidence indicates that rod death triggers multiple, non-cell-autonomous processes, which include oxidative stress and inflammation/immune...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161377/ https://www.ncbi.nlm.nih.gov/pubmed/34065385 http://dx.doi.org/10.3390/ijms22105381 |
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author | Napoli, Debora Biagioni, Martina Billeri, Federico Di Marco, Beatrice Orsini, Noemi Novelli, Elena Strettoi, Enrica |
author_facet | Napoli, Debora Biagioni, Martina Billeri, Federico Di Marco, Beatrice Orsini, Noemi Novelli, Elena Strettoi, Enrica |
author_sort | Napoli, Debora |
collection | PubMed |
description | In retinitis pigmentosa (RP), one of many possible genetic mutations causes rod degeneration, followed by cone secondary death leading to blindness. Accumulating evidence indicates that rod death triggers multiple, non-cell-autonomous processes, which include oxidative stress and inflammation/immune responses, all contributing to cone demise. Inflammation relies on local microglia and recruitment of immune cells, reaching the retina through breakdowns of the inner blood retinal barrier (iBRB). Leakage in the inner retina vasculature suggests similarly altered outer BRB, formed by junctions between retinal pigment epithelium (RPE) cells, which are crucial for retinal homeostasis, immune response, and privilege. We investigated the RPE structural integrity in three models of RP (rd9, rd10, and Tvrm4 mice) by immunostaining for zonula occludens-1 (ZO-1), an essential regulatory component of tight junctions. Quantitative image analysis demonstrated discontinuities in ZO-1 profiles in all mutants, despite different degrees of photoreceptor loss. ZO-1 interruption zones corresponded to leakage of in vivo administered, fluorescent dextran through the choroid-RPE interface, demonstrating barrier dysfunction. Dexamethasone, administered to rd10 mice for rescuing cones, also rescued RPE structure. Thus, previously undetected, stereotyped abnormalities occur in the RPE of RP mice; pharmacological targeting of inflammation supports a feedback loop leading to simultaneous protection of cones and the RPE. |
format | Online Article Text |
id | pubmed-8161377 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81613772021-05-29 Retinal Pigment Epithelium Remodeling in Mouse Models of Retinitis Pigmentosa Napoli, Debora Biagioni, Martina Billeri, Federico Di Marco, Beatrice Orsini, Noemi Novelli, Elena Strettoi, Enrica Int J Mol Sci Article In retinitis pigmentosa (RP), one of many possible genetic mutations causes rod degeneration, followed by cone secondary death leading to blindness. Accumulating evidence indicates that rod death triggers multiple, non-cell-autonomous processes, which include oxidative stress and inflammation/immune responses, all contributing to cone demise. Inflammation relies on local microglia and recruitment of immune cells, reaching the retina through breakdowns of the inner blood retinal barrier (iBRB). Leakage in the inner retina vasculature suggests similarly altered outer BRB, formed by junctions between retinal pigment epithelium (RPE) cells, which are crucial for retinal homeostasis, immune response, and privilege. We investigated the RPE structural integrity in three models of RP (rd9, rd10, and Tvrm4 mice) by immunostaining for zonula occludens-1 (ZO-1), an essential regulatory component of tight junctions. Quantitative image analysis demonstrated discontinuities in ZO-1 profiles in all mutants, despite different degrees of photoreceptor loss. ZO-1 interruption zones corresponded to leakage of in vivo administered, fluorescent dextran through the choroid-RPE interface, demonstrating barrier dysfunction. Dexamethasone, administered to rd10 mice for rescuing cones, also rescued RPE structure. Thus, previously undetected, stereotyped abnormalities occur in the RPE of RP mice; pharmacological targeting of inflammation supports a feedback loop leading to simultaneous protection of cones and the RPE. MDPI 2021-05-20 /pmc/articles/PMC8161377/ /pubmed/34065385 http://dx.doi.org/10.3390/ijms22105381 Text en © 2021 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 Napoli, Debora Biagioni, Martina Billeri, Federico Di Marco, Beatrice Orsini, Noemi Novelli, Elena Strettoi, Enrica Retinal Pigment Epithelium Remodeling in Mouse Models of Retinitis Pigmentosa |
title | Retinal Pigment Epithelium Remodeling in Mouse Models of Retinitis Pigmentosa |
title_full | Retinal Pigment Epithelium Remodeling in Mouse Models of Retinitis Pigmentosa |
title_fullStr | Retinal Pigment Epithelium Remodeling in Mouse Models of Retinitis Pigmentosa |
title_full_unstemmed | Retinal Pigment Epithelium Remodeling in Mouse Models of Retinitis Pigmentosa |
title_short | Retinal Pigment Epithelium Remodeling in Mouse Models of Retinitis Pigmentosa |
title_sort | retinal pigment epithelium remodeling in mouse models of retinitis pigmentosa |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161377/ https://www.ncbi.nlm.nih.gov/pubmed/34065385 http://dx.doi.org/10.3390/ijms22105381 |
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