Preclinical trial of the antioxidant compound hexafluoro in a zebrafish model of Usher syndrome type 1F
| dc.contributor.advisor | Phillips, Jennifer | |
| dc.contributor.advisor | Dudukovic, Nicole | |
| dc.contributor.author | Kulis, Siena | |
| dc.date.accessioned | 2023-08-18T15:54:34Z | |
| dc.date.available | 2023-08-18T15:54:34Z | |
| dc.date.issued | 2023 | |
| dc.description | 43 pages | en_US |
| dc.description.abstract | Usher syndrome (USH) is a genetic disorder that is the leading hereditary cause of deaf-blindness, affecting more than 400,000 people worldwide. Usher syndrome type 1 (USH1) is characterized by hearing loss from birth, and gradual vision loss beginning with reduced night vision in childhood. Mutations in the PCDH15 gene result in Usher Syndrome type 1F (USH1F), a subcategory of USH1. These mutations create nonfunctional versions of the protocadherin-15 protein (PCDH15) which impair its function, disrupting the structure and function of hair cells in the inner ear and photoreceptor cells in the eye. Zebrafish models of USH1F have abnormal photoreceptor structure, reduced visual function, and elevated rates of cell death, symptoms that are exacerbated by bright light. A pilot study showed that the antioxidant compound hexafluoro improved visual function in young zebrafish models of USH1F raised in dim conditions. We treated USH1F mutant fish raised in a variety of daytime light conditions with hexafluoro to understand hexafluoro’s effect in conditions that result in increased cell death. We used an optokinetic response assay to test the compound’s effect on visual function, and analyzed its effect on photoreceptor cell death by tallying the number of photoreceptors in the central region of the retina. We found that hexafluoro improved visual function and slowed photoreceptor cell death in the USH1F mutant fish raised in all light conditions. Our data indicate that hexafluoro has a stabilizing effect on photoreceptors in zebrafish USH1F models, and implicate oxidative stress as a possible mechanism behind the pathology of USH1F visual symptoms. These results support further investigation into the mechanism(s) underlying hexafluoro effects and application of this antioxidant in other models of USH. | en_US |
| dc.identifier.orcid | 0009-0007-6412-3922 | |
| dc.identifier.uri | https://hdl.handle.net/1794/28684 | |
| dc.language.iso | en_US | |
| dc.publisher | University of Oregon | |
| dc.rights | CC BY-NC-ND 4.0 | |
| dc.subject | Usher syndrome | en_US |
| dc.subject | Zebrafish | en_US |
| dc.subject | hexafluoro | en_US |
| dc.subject | antioxidant | en_US |
| dc.subject | blindness | en_US |
| dc.title | Preclinical trial of the antioxidant compound hexafluoro in a zebrafish model of Usher syndrome type 1F | |
| dc.type | Thesis/Dissertation |