Retina damage or disease in humans often leads to reactive gliosis, preventing the formation of new cells and resulting in visual impairment or blindness. Currently, treatments are being developed to stimulate repair or replacement of lost retinal neurons by intravitreal injection of stem cells or retina precursors. Though improving, these therapies are inefficient and not yet capable of fully restoring vision. In contrast to mammals, the zebrafish retina is capable of spontaneous regeneration upon damage, using Müller glia (MG) derived progenitors. Understanding how zebrafish MG initiate regeneration may allow for the discovery of treatments that prompt mammalian retinas to regenerate. Here I show that inhibition of GABA signaling facilitates MG proliferation and initiation of retina regeneration. Using pharmacological and genetic approaches to disrupt neurotransmitter signaling, I demonstrate that GABAA receptor inhibition stimulates spontaneous regeneration in undamaged zebrafish retinas while GABAA receptor activation inhibits regeneration in damaged zebrafish retinas. This is the first evidence that neurotransmitters control retina regeneration in zebrafish through an evolutionarily conserved mechanism of neurogenesis.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-07272016-094036 |
| Date | 27 July 2016 |
| Creators | Rao, Mahesh Badeti |
| Contributors | Ronald Emeson, Antonis Rokas, James G. Patton, Douglas McMahon, James G. Patton, Antonis Rokas, Ronald Emeson, Douglas McMahon |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-07272016-094036/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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