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Coordinated Intervention of Microglial and Müller Cells in Light-Induced Retinal Degeneration

PURPOSE: To analyze the role of microglial and Müller cells in the formation of rings of photoreceptor degeneration caused by phototoxicity. METHODS: Two-month-old Sprague-Dawley rats were exposed to light and processed 1, 2, or 3 months later. Retinas were dissected as whole-mounts, immunodetected...

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Autores principales: Di Pierdomenico, Johnny, Martínez-Vacas, Ana, Hernández-Muñoz, Daniel, Gómez-Ramírez, Ana M., Valiente-Soriano, Francisco Javier, Agudo-Barriuso, Marta, Vidal-Sanz, Manuel, Villegas-Pérez, María P., García-Ayuso, Diego
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401701/
https://www.ncbi.nlm.nih.gov/pubmed/32232352
http://dx.doi.org/10.1167/iovs.61.3.47
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author Di Pierdomenico, Johnny
Martínez-Vacas, Ana
Hernández-Muñoz, Daniel
Gómez-Ramírez, Ana M.
Valiente-Soriano, Francisco Javier
Agudo-Barriuso, Marta
Vidal-Sanz, Manuel
Villegas-Pérez, María P.
García-Ayuso, Diego
author_facet Di Pierdomenico, Johnny
Martínez-Vacas, Ana
Hernández-Muñoz, Daniel
Gómez-Ramírez, Ana M.
Valiente-Soriano, Francisco Javier
Agudo-Barriuso, Marta
Vidal-Sanz, Manuel
Villegas-Pérez, María P.
García-Ayuso, Diego
author_sort Di Pierdomenico, Johnny
collection PubMed
description PURPOSE: To analyze the role of microglial and Müller cells in the formation of rings of photoreceptor degeneration caused by phototoxicity. METHODS: Two-month-old Sprague-Dawley rats were exposed to light and processed 1, 2, or 3 months later. Retinas were dissected as whole-mounts, immunodetected for microglial cells, Müller cells, and S- and L/M-cones and analyzed using fluorescence, thunder imaging, and confocal microscopy. Cone populations were automatically counted and isodensity maps constructed to document cone topography. RESULTS: Phototoxicity causes a significant progressive loss of S- and L/M-cones of up to 68% and 44%, respectively, at 3 months after light exposure (ALE). One month ALE, we observed rings of cone degeneration in the photosensitive area of the superior retina. Two and 3 months ALE, these rings had extended to the central and inferior retina. Within the rings of cone degeneration, there were degenerating cones, often activated microglial cells, and numerous radially oriented processes of Müller cells that showed increased expression of intermediate filaments. Between 1 and 3 months ALE, the rings coalesced, and at the same time the microglial cells resumed a mosaic-like distribution, and there was a decrease of Müller cell gliosis at the areas devoid of cones. CONCLUSIONS: Light-induced photoreceptor degeneration proceeds with rings of cone degeneration, as observed in inherited retinal degenerations in which cone death is secondary to rod degeneration. The spatiotemporal relationship of cone death microglial cell activation and Müller cell gliosis within the rings of cone degeneration suggests that, although both glial cells are involved in the formation of the rings, they may have coordinated actions and, while microglial cells may be more involved in photoreceptor phagocytosis, Müller cells may be more involved in cone and microglial cell migration, retinal remodeling and glial seal formation.
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spelling pubmed-74017012020-08-18 Coordinated Intervention of Microglial and Müller Cells in Light-Induced Retinal Degeneration Di Pierdomenico, Johnny Martínez-Vacas, Ana Hernández-Muñoz, Daniel Gómez-Ramírez, Ana M. Valiente-Soriano, Francisco Javier Agudo-Barriuso, Marta Vidal-Sanz, Manuel Villegas-Pérez, María P. García-Ayuso, Diego Invest Ophthalmol Vis Sci Retinal Cell Biology PURPOSE: To analyze the role of microglial and Müller cells in the formation of rings of photoreceptor degeneration caused by phototoxicity. METHODS: Two-month-old Sprague-Dawley rats were exposed to light and processed 1, 2, or 3 months later. Retinas were dissected as whole-mounts, immunodetected for microglial cells, Müller cells, and S- and L/M-cones and analyzed using fluorescence, thunder imaging, and confocal microscopy. Cone populations were automatically counted and isodensity maps constructed to document cone topography. RESULTS: Phototoxicity causes a significant progressive loss of S- and L/M-cones of up to 68% and 44%, respectively, at 3 months after light exposure (ALE). One month ALE, we observed rings of cone degeneration in the photosensitive area of the superior retina. Two and 3 months ALE, these rings had extended to the central and inferior retina. Within the rings of cone degeneration, there were degenerating cones, often activated microglial cells, and numerous radially oriented processes of Müller cells that showed increased expression of intermediate filaments. Between 1 and 3 months ALE, the rings coalesced, and at the same time the microglial cells resumed a mosaic-like distribution, and there was a decrease of Müller cell gliosis at the areas devoid of cones. CONCLUSIONS: Light-induced photoreceptor degeneration proceeds with rings of cone degeneration, as observed in inherited retinal degenerations in which cone death is secondary to rod degeneration. The spatiotemporal relationship of cone death microglial cell activation and Müller cell gliosis within the rings of cone degeneration suggests that, although both glial cells are involved in the formation of the rings, they may have coordinated actions and, while microglial cells may be more involved in photoreceptor phagocytosis, Müller cells may be more involved in cone and microglial cell migration, retinal remodeling and glial seal formation. The Association for Research in Vision and Ophthalmology 2020-03-30 /pmc/articles/PMC7401701/ /pubmed/32232352 http://dx.doi.org/10.1167/iovs.61.3.47 Text en Copyright 2020 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
Di Pierdomenico, Johnny
Martínez-Vacas, Ana
Hernández-Muñoz, Daniel
Gómez-Ramírez, Ana M.
Valiente-Soriano, Francisco Javier
Agudo-Barriuso, Marta
Vidal-Sanz, Manuel
Villegas-Pérez, María P.
García-Ayuso, Diego
Coordinated Intervention of Microglial and Müller Cells in Light-Induced Retinal Degeneration
title Coordinated Intervention of Microglial and Müller Cells in Light-Induced Retinal Degeneration
title_full Coordinated Intervention of Microglial and Müller Cells in Light-Induced Retinal Degeneration
title_fullStr Coordinated Intervention of Microglial and Müller Cells in Light-Induced Retinal Degeneration
title_full_unstemmed Coordinated Intervention of Microglial and Müller Cells in Light-Induced Retinal Degeneration
title_short Coordinated Intervention of Microglial and Müller Cells in Light-Induced Retinal Degeneration
title_sort coordinated intervention of microglial and müller cells in light-induced retinal degeneration
topic Retinal Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401701/
https://www.ncbi.nlm.nih.gov/pubmed/32232352
http://dx.doi.org/10.1167/iovs.61.3.47
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