Glaucoma is a prevalent retinal neurodegenerative disease that is characterized by progressive visual field loss, leading to eventual blindness. The main risk factor for glaucoma is elevated intraocular pressure (IOP) which results in the damage and death of retinal ganglion cells (RGCs) and their axons. The endpoint of the disease is the death of these cells by apoptosis; therefore, blocking the activation of apoptosis was hypothesized to be an effective therapy. Magnetic microbeads were injected into the eyes of mice to induce a model of ocular hypertension. Apoptosis was targeted through viral-mediated ocular delivery of the X-linked inhibitor of apoptosis (XIAP) gene, a potent caspase inhibitor. XIAP overexpression resulted in significant protection of ganglion cell somal and axonal function in glaucomatous eyes, and their optic nerves showed preservation of axon density, counts, and myelination, suggesting XIAP was able to provide both structural and functional protection. The results of these experiments provide proof-of-principle for XIAP’s efficacy as a neuroprotective treatment for glaucoma and are an important step forward in evaluating its full therapeutic potential.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/38699 |
| Date | 15 January 2019 |
| Creators | Visuvanathan, Shagana |
| Contributors | Tsilfidis, Catherine |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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