Luis, Joshua;
(2023)
Galectins-1 and -3 Functions in Müller Glia during Retinal Development and Degeneration.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Within the retina, Müller glial cells (MGCs) are central regulators of metabolic homeostasis during normal function and during pathogenic states. MGCs are major producers of Galectins (Gal) -1 and -3, carbohydrate-binding proteins which have been found to be key regulators of various cellular processes. This study aimed to investigate the potential roles of Gal-1 and -3 during inflammatory stimuli, as well as during models of retinal development and degeneration. Treatment of MIO-M1 cells with the pro-inflammatory cytokine IL-1 resulted in significant upregulation of Gal-1 (p<.01) and the sialylation enzyme ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (p<.01), whereas treatment with TGF-β significantly reduced the production of Gal-3 (p<.001) but had no significant effect on ST6 beta-galactoside alpha-2,3-sialyltransferase 1 (p>.05). Inhibition of Gal-3 by siRNA increased the rate of MIO-M1 cell proliferation (p<.001). TGF-β2 treatment increased the rate of migration of MIO-M1 cells (p<.01), but this effect was nullified following Gal-3 siRNA inhibition. During retinal organoid development, Gal-1 mRNA and protein expression peaked between days 10 and 30, whilst Gal-3 mRNA and protein expression increased steadily to peak at the end of the experimental period of 90 days. Using an experimental model of intraocular pressure elevation, Gal-3 protein expression was found to be upregulated in anterior chamber tissues including the iridocorneal angle and iris. Additional studies in a rodent model of optic neuropathy showed that MGC derived extracellular vesicles were effective in partially restoring retinal function at 2 weeks after treatment (p<.001). This effect, however, was not maintained at 4 weeks (p>.05), for which further investigations are merited. Although the current study has provided a better understanding of the roles of Galectins during retinal development and degeneration, additional studies are warranted to elucidate the wider roles of Gal-1 and -3 during retinal degenerative diseases and explore any potential therapeutic applications of these molecules.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Galectins-1 and -3 Functions in Müller Glia during Retinal Development and Degeneration |
| 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/10163948 |
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