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Choroidal-scleral cell interplay and the regulation of scleral biomechanics

Ren, Yuyi; (2023) Choroidal-scleral cell interplay and the regulation of scleral biomechanics. Masters thesis (M.Phil), UCL (University College London). Green open access

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Abstract

Worldwide prevalence and severity of myopia have increased dramatically nowadays. High myopia and its irreversible associated eye elongation increase the risk of sight-threatening conditions. However, the exact mechanisms that drive myopia progression are still unknown. Myopia almost exclusively occurs in childhood, suggesting the adult sclera is functionally different from the young sclera. During myopia progression, the sclera becomes thinner and more elastic, and the composition of its scleral extracellular matrix changes. Similarly, the choroid is thinner and accommodation-induced choroidal secreted factors are linked to tissue biomechanics that may regulate scleral remodelling and eye elongation. Thus, we hypothesize that signals from the choroid are crucial to the regulation of scleral biomechanics. In addition, light exposure and subsequent dopamine release may regulate scleral remodelling and eye elongation, and myopia development and progression could be induced by near work. We used human primary fibroblasts isolated from the sclera and choroid of donor eyes from different ages and antero-posterior positions to test our hypothesis. We found that paediatric scleral fibroblastsembedded in the 3D collagen gels had greater contractility than adult ones, particularly those from the anterior part of the sclera. Scleral fibroblasts’ ability to contract collagen gels was enhanced following stimulation with the choroid-conditioned medium, and this promotion was not due to an increase in proliferation or change in a-SMA expression. Furthermore, the ability of choroid conditioned medium to stimulate scleral fibroblasts was completely abolished when choroid cells were treated with dopamine. This suggests that normal scleral development is regulated by a balance between positive biochemical signals from the choroid, and negative signals resulting from a direct effect of retina-derived dopamine on the choroid cells. These findings may help improve clinical practice to control myopia development and progression in the future.

Type: Thesis (Masters)
Qualification: M.Phil
Title: Choroidal-scleral cell interplay and the regulation of scleral biomechanics
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/10163952
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