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Article

Retinal Pigment Epithelium Remodeling in Mouse Models of Retinitis Pigmentosa

1
CNR Neuroscience Institute, 56124 Pisa, Italy
2
Department of Biology, University of Pisa, 56126 Pisa, Italy
3
Regional Doctorate School in Neuroscience, Universities of Florence, Pisa and Siena, 50139 Florence, Italy
*
Authors to whom correspondence should be addressed.
Present Address: Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, Italy.
Academic Editor: Valeria Marigo
Int. J. Mol. Sci. 2021, 22(10), 5381; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105381
Received: 26 April 2021 / Revised: 13 May 2021 / Accepted: 17 May 2021 / Published: 20 May 2021
(This article belongs to the Special Issue Retinal Degeneration: Molecular Mechanism, Pathogenesis and Treatment)
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. View Full-Text
Keywords: retinitis pigmentosa; retinal pigment epithelium; rd9 mouse; rd10 mouse; Tvrm4 mouse; blood retinal barrier; zonula occludens; immunocytochemistry; dextranes retinitis pigmentosa; retinal pigment epithelium; rd9 mouse; rd10 mouse; Tvrm4 mouse; blood retinal barrier; zonula occludens; immunocytochemistry; dextranes
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MDPI and ACS Style

Napoli, D.; Biagioni, M.; Billeri, F.; Di Marco, B.; Orsini, N.; Novelli, E.; Strettoi, E. Retinal Pigment Epithelium Remodeling in Mouse Models of Retinitis Pigmentosa. Int. J. Mol. Sci. 2021, 22, 5381. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105381

AMA Style

Napoli D, Biagioni M, Billeri F, Di Marco B, Orsini N, Novelli E, Strettoi E. Retinal Pigment Epithelium Remodeling in Mouse Models of Retinitis Pigmentosa. International Journal of Molecular Sciences. 2021; 22(10):5381. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105381

Chicago/Turabian Style

Napoli, Debora, Martina Biagioni, Federico Billeri, Beatrice Di Marco, Noemi Orsini, Elena Novelli, and Enrica Strettoi. 2021. "Retinal Pigment Epithelium Remodeling in Mouse Models of Retinitis Pigmentosa" International Journal of Molecular Sciences 22, no. 10: 5381. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105381

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