Exploring the Roles of Muller Glia and Activated Leukocyte Cell Adhesion Molecule A in Zebrafish Retinal Regeneration
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Case Western Reserve University School of Graduate Studies / OhioLINK
2021
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=case1607705752486913 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-case16077057524869132021-08-03T07:16:40Z Exploring the Roles of Muller Glia and Activated Leukocyte Cell Adhesion Molecule A in Zebrafish Retinal Regeneration Allan, Kristin Ophthalmology Biomedical Research Cellular Biology Molecular Biology Muller glia retina zebrafish regeneration Alcama In contrast to humans, animals such as zebrafish are able to regenerate their retinas after injury. Retinal cells called Muller glia facilitate regeneration in fish, yet contribute to scar formation in humans. Zebrafish Muller glia respond to injury by dedifferentiating and undergoing an asymmetric cell division, giving rise to a Muller glia and a proliferating progenitor cell. Subsequent progenitor cell migration and differentiation restores proper retina structure and function. The mechanisms governing the migration and functional integration of these progenitor cells, however, are not yet understood. A cell-surface adhesion molecule called Alcama, a novel marker of activated zebrafish Muller glia, contributes to cell migration, ganglion cell axonal guidance, and retinal lamination during development in both fish and mice. We hypothesize that Alcama, expressed in Muller glia following injury, facilitates the migration of progenitor cells and is important for zebrafish retinal regeneration. Here, we describe how Muller glia were isolated from the heterogenic population of retinal cells in Tg(apoe:gfp) fish with fluorescence activated cell sorting (FACS). The GFP-high population of cells represent Muller glia, which only express Alcama after injury, a pattern that is unique to this population. We have previously shown that proliferating progenitor cells migrate from the inner to outer nuclear layer of the retina following injury under normal conditions. To determine Alcama’s role in regeneration, we knocked down its expression in the adult retina with in vivo electroporation of antisense morpholinos targeting Alcama. Using EdU lineage tracing, we have observed significant differences between control and Alcama morpholino-treated eyes in the proportion of EdU-positive cells in the inner and outer nuclear layers over time, suggesting that Alcama is playing a role in progenitor cell migration during regeneration. We have also seen a delay in overall regeneration after Alcama morpholino treatment using in vivo SLO imaging to measure lesion area over time, as well as a reduction in regenerated cone cell density using immunohistochemistry. This work will contribute to a deeper understanding of mechanisms governing regeneration in zebrafish for future translation into human therapies to restore lost vision. 2021-01-22 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1607705752486913 http://rave.ohiolink.edu/etdc/view?acc_num=case1607705752486913 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Ophthalmology Biomedical Research Cellular Biology Molecular Biology Muller glia retina zebrafish regeneration Alcama |
| spellingShingle |
Ophthalmology Biomedical Research Cellular Biology Molecular Biology Muller glia retina zebrafish regeneration Alcama Allan, Kristin Exploring the Roles of Muller Glia and Activated Leukocyte Cell Adhesion Molecule A in Zebrafish Retinal Regeneration |
| author |
Allan, Kristin |
| author_facet |
Allan, Kristin |
| author_sort |
Allan, Kristin |
| title |
Exploring the Roles of Muller Glia and Activated Leukocyte Cell Adhesion Molecule A in Zebrafish Retinal Regeneration |
| title_short |
Exploring the Roles of Muller Glia and Activated Leukocyte Cell Adhesion Molecule A in Zebrafish Retinal Regeneration |
| title_full |
Exploring the Roles of Muller Glia and Activated Leukocyte Cell Adhesion Molecule A in Zebrafish Retinal Regeneration |
| title_fullStr |
Exploring the Roles of Muller Glia and Activated Leukocyte Cell Adhesion Molecule A in Zebrafish Retinal Regeneration |
| title_full_unstemmed |
Exploring the Roles of Muller Glia and Activated Leukocyte Cell Adhesion Molecule A in Zebrafish Retinal Regeneration |
| title_sort |
exploring the roles of muller glia and activated leukocyte cell adhesion molecule a in zebrafish retinal regeneration |
| publisher |
Case Western Reserve University School of Graduate Studies / OhioLINK |
| publishDate |
2021 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=case1607705752486913 |
| work_keys_str_mv |
AT allankristin exploringtherolesofmullergliaandactivatedleukocytecelladhesionmoleculeainzebrafishretinalregeneration |
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