Characterization of retinal regeneration in adult zebrafish following multiple rounds of phototoxic lesion

Müller glia in the zebrafish retina respond to retinal damage by re-entering the cell cycle, which generates large numbers of retinal progenitors that ultimately replace the lost neurons. In this study we compared the regenerative outcomes of adult zebrafish exposed to one round of phototoxic treatm...

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Main Authors: Alexandra H. Ranski, Ashley C. Kramer, Gregory W. Morgan, Jennifer L. Perez, Ryan Thummel
Format: Article
Language:English
Published: PeerJ Inc. 2018-09-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/5646.pdf
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author Alexandra H. Ranski
Ashley C. Kramer
Gregory W. Morgan
Jennifer L. Perez
Ryan Thummel
author_facet Alexandra H. Ranski
Ashley C. Kramer
Gregory W. Morgan
Jennifer L. Perez
Ryan Thummel
author_sort Alexandra H. Ranski
collection DOAJ
description Müller glia in the zebrafish retina respond to retinal damage by re-entering the cell cycle, which generates large numbers of retinal progenitors that ultimately replace the lost neurons. In this study we compared the regenerative outcomes of adult zebrafish exposed to one round of phototoxic treatment with adult zebrafish exposed to six consecutive rounds of phototoxic treatment. We observed that Müller glia continued to re-enter the cell cycle to produce clusters of retinal progenitors in zebrafish exposed to multiple rounds of phototoxic light. Some abnormalities were noted, however. First, we found that retinas exposed to multiple rounds of damage exhibited a greater loss of photoreceptors at 36 hours of light damage than retinas that were exposed to their first round of light damage. In addition, we found that Müller glia appeared to have an increase in the acute gliotic response in retinas exposed to multiple rounds of light treatment. This was evidenced by cellular hypertrophy, changes in GFAP cellular localization, and transient increases in stat3 and gfap expression. Finally, following the sixth round of phototoxic lesion, we observed a significant increase in mis-localized HuC/D-positive amacrine and ganglion cells in the inner plexiform layer and outer retina, and a decreased number of regenerated blue cone photoreceptors. These data add to recent findings that retinal regeneration in adult zebrafish occurs concomitant with Müller glia reactivity and can result in the generation of aberrant neurons. These data are also the first to demonstrate that Müller glia appear to modify their phenotype in response to multiple rounds of phototoxic lesion, exhibiting an increase in acute gliosis while maintaining a remarkable capacity for long-term regeneration of photoreceptors.
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spelling doaj.art-579a1ae14dac4c148e00227edacc1bcc2023-12-03T10:37:34ZengPeerJ Inc.PeerJ2167-83592018-09-016e564610.7717/peerj.5646Characterization of retinal regeneration in adult zebrafish following multiple rounds of phototoxic lesionAlexandra H. Ranski0Ashley C. Kramer1Gregory W. Morgan2Jennifer L. Perez3Ryan Thummel4Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, USADepartment of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, USADepartment of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, USADepartment of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, USADepartment of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, USAMüller glia in the zebrafish retina respond to retinal damage by re-entering the cell cycle, which generates large numbers of retinal progenitors that ultimately replace the lost neurons. In this study we compared the regenerative outcomes of adult zebrafish exposed to one round of phototoxic treatment with adult zebrafish exposed to six consecutive rounds of phototoxic treatment. We observed that Müller glia continued to re-enter the cell cycle to produce clusters of retinal progenitors in zebrafish exposed to multiple rounds of phototoxic light. Some abnormalities were noted, however. First, we found that retinas exposed to multiple rounds of damage exhibited a greater loss of photoreceptors at 36 hours of light damage than retinas that were exposed to their first round of light damage. In addition, we found that Müller glia appeared to have an increase in the acute gliotic response in retinas exposed to multiple rounds of light treatment. This was evidenced by cellular hypertrophy, changes in GFAP cellular localization, and transient increases in stat3 and gfap expression. Finally, following the sixth round of phototoxic lesion, we observed a significant increase in mis-localized HuC/D-positive amacrine and ganglion cells in the inner plexiform layer and outer retina, and a decreased number of regenerated blue cone photoreceptors. These data add to recent findings that retinal regeneration in adult zebrafish occurs concomitant with Müller glia reactivity and can result in the generation of aberrant neurons. These data are also the first to demonstrate that Müller glia appear to modify their phenotype in response to multiple rounds of phototoxic lesion, exhibiting an increase in acute gliosis while maintaining a remarkable capacity for long-term regeneration of photoreceptors.https://peerj.com/articles/5646.pdfStem cellMüller gliaZebrafishPhotoreceptorRegenerationGliosis
spellingShingle Alexandra H. Ranski
Ashley C. Kramer
Gregory W. Morgan
Jennifer L. Perez
Ryan Thummel
Characterization of retinal regeneration in adult zebrafish following multiple rounds of phototoxic lesion
PeerJ
Stem cell
Müller glia
Zebrafish
Photoreceptor
Regeneration
Gliosis
title Characterization of retinal regeneration in adult zebrafish following multiple rounds of phototoxic lesion
title_full Characterization of retinal regeneration in adult zebrafish following multiple rounds of phototoxic lesion
title_fullStr Characterization of retinal regeneration in adult zebrafish following multiple rounds of phototoxic lesion
title_full_unstemmed Characterization of retinal regeneration in adult zebrafish following multiple rounds of phototoxic lesion
title_short Characterization of retinal regeneration in adult zebrafish following multiple rounds of phototoxic lesion
title_sort characterization of retinal regeneration in adult zebrafish following multiple rounds of phototoxic lesion
topic Stem cell
Müller glia
Zebrafish
Photoreceptor
Regeneration
Gliosis
url https://peerj.com/articles/5646.pdf
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