Establishing zebrafish, Danio rerio, as a genetic model for glaucoma

Umali, Jurgienne Arizza Gomez (2020) Establishing zebrafish, Danio rerio, as a genetic model for glaucoma. Masters thesis, Memorial University of Newfoundland.

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Abstract

Glaucoma is characterized by retinal ganglion cell (RGC) death, leading to vision loss. The leading risk factor for glaucoma is elevated intraocular pressure (IOP), however 30 percent of patients have IOP within the reference range, suggesting IOP-independent mechanisms underlying disease pathogenesis. Mutations in the forkhead transcription factor FOXC1 cause Axenfeld-Rieger Syndrome with early-onset or congenital glaucoma, however the mechanism by which this occurs is not fully understood. We assessed RGC number and optic nerve width in embryonic zebrafish with inhibition of foxc1a and foxc1b via antisense morpholinos and CRISPR-mediated mutation. At 5 days post fertilization, foxc1b-/- embryos injected with foxc1a morpholinos have decreased cells in the RGC layer and thinner optic nerves. In situ hybridization shows loss of foxc1 results in dysregulation of atonal homolog 7 (atoh7), a gene involved in RGC differentiation. Overall, we propose that altered RGC differentiation interacts with other risk factors to influence FOXC1-associated glaucoma pathogenesis.

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