Vision restoration in a newly characterized porcine model of traumatic optic neuropathy
Abstract/Contents
- Abstract
- Traumatic optic neuropathy (TON) is a devastating condition that can occur after blunt or penetrating trauma to the head, leading to visual impairment or blindness. Despite these debilitating effects, no clinically available therapeutic targets neuroprotection or promotes axon regeneration in this or any optic neuropathy. Limited data in large animal models is a major obstacle to advancing treatments toward clinical therapeutics. In Chapter 1, I review pathophysiology, epidemiology, and animal models of TON. In Chapter 2, I refine a newly developed surgical model of TON in Yucatan minipigs. First, we validate the model by demonstrating visual impairment by flash visual-evoked potential and retinal ganglion cell degeneration and death. Next, we develop and optimize a delivery method and non-toxic dosing of intravitreal brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP). Finally, we show that intravitreal injection of BDNF and cAMP rescues visual function and protects against retinal ganglion cell death and optic nerve axon degeneration. In Chapter 3, we determine the time course of porcine neutralizing antibody development against a virally-mediated gene therapy. We demonstrate that, despite antibody production in response to a primary recombinant AAV2 exposure, a secondary exposure to AAV2 may result in transduced cells. In Chapter 4, we perform two-photon imaging with single-cell resolution of fluorescently labeled RGCs in a whole explanted porcine eye. In Chapter 5, I provide concluding concepts and discuss future directions. Together these data in a pre-clinical large animal model advance our understanding of and ability to model TON and further identify and develop candidate clinical therapeutics.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Heng, Kathleen |
|---|---|
| Degree supervisor | Goldberg, Jeffrey L |
| Thesis advisor | Goldberg, Jeffrey L |
| Thesis advisor | Buckmaster, Paul S |
| Thesis advisor | Hu, Yang |
| Thesis advisor | Wang, Sui, 1982- |
| Degree committee member | Buckmaster, Paul S |
| Degree committee member | Hu, Yang |
| Degree committee member | Wang, Sui, 1982- |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Neurosciences Program |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Kathleen Heng. |
|---|---|
| Note | Submitted to the Neurosciences Program. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/vx955rb8677 |
Access conditions
- Copyright
- © 2023 by Kathleen Heng
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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