Shinhmar, Harpreet;
(2023)
Light as a biological modulator. A cross species study.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Normal ageing is associated with a decline in the quality of mitochondria and its function. Mitochondrial dysfunction is affiliated with reduced production of ATP, a characteristic feature of ageing and disease. Therefore, mitochondria are key targets of therapeutic agents. Aged mitochondrial function can be improved optically by longwavelength light (650-900nm) exposure, resulting in increased ATP production and reduced ROS. These changes translate into improved functionality from flies to humans. This thesis aims to assess the contribution of mitochondrial dysfunction in ageing, especially in a metabolically demanding environment such as the retina; and investigate the effects of 670nm light exposure in improving aged function. This will be achieved using three animal models flies, mice, and primates, before translating findings to humans. Flies revealed a decline of mitochondrial function with age and shifts of these functions across the day. The functional shifts revealed optimal timings for 670nm exposure in improving mitochondrial function. The ageing mouse retina showed changes in mitochondrial dynamics that altered with 670nm exposure, especially in the photoreceptor layer. Mitochondrial biogenesis declined with age, and the CFH-/- mouse revealed further disruptions of this process. The immune system, by assessing cytokine patterns, demonstrated a decline with age which altered following 670nm exposure. The ageing primate retina revealed a decline in mitochondrial membrane potentials and ultrastructure. Cone cells are characterised by high mitochondrial density, they demonstrated altered patterns of mitochondrial dynamics with age. Translating evidence from animal models to humans revealed a decline in electroretinograms and colour vision with age. Older subjects showed improvement to visual function following 2 weeks of 670nm exposure. Investigations of single exposures of red light demonstrated improved colour vision only when light was delivered in the morning, similar to findings in flies. This thesis was able to demonstrate the universal nature of mitochondrial ageing across species and how this can be ameliorated with exposure to long-wavelength light.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Light as a biological modulator. A cross species study |
| Open access status: | An open access version is available from UCL Discovery |
| 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. |
| 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/10179188 |
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