Hill, Daniel Charles;
(2023)
Applications of Retinal Fluorescence and Annexin A5 in the Detection and Prevention of Neurodegeneration.
Doctoral thesis (Ph.D), UCL (University College London).
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THESIS FOR PUBLIC SUBMISSION.pdf - Accepted Version Access restricted to UCL open access staff until 1 January 2027. Download (8MB) |
Abstract
The present body of work aimed to advance tools for the detection and prevention of neurodegeneration, using Annexin A5 and retinal fluorescence. Namely, advancement of the use of fluorescent Annexin A5 for the in vivo and in vitro detection of cell stress, investigating curcumin as a fluorescent retinal diagnostic tool for Alzheimer’s disease, and developing a drug delivery system leveraging the properties of Annexin A5. A protocol has been established for high-yield cost-efficient production and subsequent fluorescent conjugation of a novel, genetically modified recombinant Annexin A5 molecule (UCL-Annexin). The intranasal route of delivery has been used for the first time to administer fluorescent Annexin A5 (UCL-DARC; detection of apoptosing retinal cells) in vivo to non-invasively label and image (via confocal scanning laser ophthalmoscopy; cSLO) stressed and apoptosing retinal cells in various rodent models of retinal damage. Using multiple wavelengths of UCL-DARC in vitro, the reversal of phosphatidylserine externalisation in response to recovery from cell stress has been achieved for the first time in a manner applicable to in vivo studies. Intranasal administration of a concentrated formulation of the fluorescent amyloid-beta-binding compound curcumin has been used to demonstrate disease-dependent retinal fluorescence in vivo (imaged by cSLO) and ex vivo (measured with fluorescence microscopy) in transgenic Alzheimer mice. The novel pairing of this formulation and administration route provides evidence to support the development of this emergent approach to Alzheimer's disease diagnosis.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Applications of Retinal Fluorescence and Annexin A5 in the Detection and Prevention of Neurodegeneration |
| Language: | English |
| Additional information: | Copyright © The Author 2023. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| Keywords: | Annexin, Annexin A5, DARC, Alzheimer's, Liposomes, ADC, Apoptosis, Cell stress, Phosphatidylserine |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10183186 |
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