Inhibition of GABAA-ρ receptors induces retina regeneration in zebrafish
A potential treatment for retinal diseases is to induce an endogenous Müller glia (MG)-derived regenerative response to replace damaged neurons. In contrast to mammalian MG, zebrafish MG are capable of mediating spontaneous regeneration. We seek to define the mechanisms that enable retina regenerati...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2021-01-01
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| Series: | Neural Regeneration Research |
| Subjects: | |
| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2021;volume=16;issue=2;spage=367;epage=374;aulast=Kent |
| _version_ | 1818341089482899456 |
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| author | Matthew R Kent Nergis Kara James G Patton |
| author_facet | Matthew R Kent Nergis Kara James G Patton |
| author_sort | Matthew R Kent |
| collection | DOAJ |
| description | A potential treatment for retinal diseases is to induce an endogenous Müller glia (MG)-derived regenerative response to replace damaged neurons. In contrast to mammalian MG, zebrafish MG are capable of mediating spontaneous regeneration. We seek to define the mechanisms that enable retina regeneration in zebrafish in order to identify therapeutic targets to induce mammalian retina regeneration. We previously used pharmacological and genetic methods to inhibit gamma aminobutyric acid A (GABAA) receptors in undamaged zebrafish retinas and showed that such inhibition could induce initiation of retina regeneration, as measured by the dedifferentiation of MG and the appearance of MG-derived proliferating progenitor cells. Here, we show that inhibition of a pharmacologically distinct subset of GABAA receptors (GABAA-ρ) can also induce retina regeneration. Dual inhibition of both GABA receptor subtypes led to enhanced retina regeneration. Gene expression analyses indicate that inhibition of GABAA-ρ receptors induces a canonical retinal regenerative response. Our results support a model in which decreased levels of GABA, such as would occur after retinal cell death or damage, induce dedifferentiation of MG and the generation of proliferating progenitor cells during zebrafish retina regeneration. Animal experiments were approved by the Vanderbilt's Institutional Animal Care and Use Committee (Protocol M1800200) on January 29, 2019. |
| first_indexed | 2024-12-13T15:53:15Z |
| format | Article |
| id | doaj.art-3e9c5b6f8f164fee91d4d4ae71e7e1df |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-12-13T15:53:15Z |
| publishDate | 2021-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-3e9c5b6f8f164fee91d4d4ae71e7e1df2022-12-21T23:39:23ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742021-01-0116236737410.4103/1673-5374.286972Inhibition of GABAA-ρ receptors induces retina regeneration in zebrafishMatthew R KentNergis KaraJames G PattonA potential treatment for retinal diseases is to induce an endogenous Müller glia (MG)-derived regenerative response to replace damaged neurons. In contrast to mammalian MG, zebrafish MG are capable of mediating spontaneous regeneration. We seek to define the mechanisms that enable retina regeneration in zebrafish in order to identify therapeutic targets to induce mammalian retina regeneration. We previously used pharmacological and genetic methods to inhibit gamma aminobutyric acid A (GABAA) receptors in undamaged zebrafish retinas and showed that such inhibition could induce initiation of retina regeneration, as measured by the dedifferentiation of MG and the appearance of MG-derived proliferating progenitor cells. Here, we show that inhibition of a pharmacologically distinct subset of GABAA receptors (GABAA-ρ) can also induce retina regeneration. Dual inhibition of both GABA receptor subtypes led to enhanced retina regeneration. Gene expression analyses indicate that inhibition of GABAA-ρ receptors induces a canonical retinal regenerative response. Our results support a model in which decreased levels of GABA, such as would occur after retinal cell death or damage, induce dedifferentiation of MG and the generation of proliferating progenitor cells during zebrafish retina regeneration. Animal experiments were approved by the Vanderbilt's Institutional Animal Care and Use Committee (Protocol M1800200) on January 29, 2019.http://www.nrronline.org/article.asp?issn=1673-5374;year=2021;volume=16;issue=2;spage=367;epage=374;aulast=Kentgamma aminobutyric acid; morpholino; müller glia; neurotransmitter; regeneration; retina; stem cells; zebrafish |
| spellingShingle | Matthew R Kent Nergis Kara James G Patton Inhibition of GABAA-ρ receptors induces retina regeneration in zebrafish Neural Regeneration Research gamma aminobutyric acid; morpholino; müller glia; neurotransmitter; regeneration; retina; stem cells; zebrafish |
| title | Inhibition of GABAA-ρ receptors induces retina regeneration in zebrafish |
| title_full | Inhibition of GABAA-ρ receptors induces retina regeneration in zebrafish |
| title_fullStr | Inhibition of GABAA-ρ receptors induces retina regeneration in zebrafish |
| title_full_unstemmed | Inhibition of GABAA-ρ receptors induces retina regeneration in zebrafish |
| title_short | Inhibition of GABAA-ρ receptors induces retina regeneration in zebrafish |
| title_sort | inhibition of gabaa ρ receptors induces retina regeneration in zebrafish |
| topic | gamma aminobutyric acid; morpholino; müller glia; neurotransmitter; regeneration; retina; stem cells; zebrafish |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2021;volume=16;issue=2;spage=367;epage=374;aulast=Kent |
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