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Deriving an in vitro source of canine corneal stromal cells for future studies of corneal disease and therapeutic applications

Kafarnik, Christiane; (2022) Deriving an in vitro source of canine corneal stromal cells for future studies of corneal disease and therapeutic applications. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

The cornea is the transparent tissue located at the front of the eye, that transmits and refracts light onto the retina. Despite great advances in corneal stem cell biology in human and laboratory animal research, no information is available in dogs. Corneal pathology, as corneal crystalline dystrophy has a prevalence of up to 15% and has been described in eight different canine breeds. Cholesterol and phospholipids are deposited in the stroma, similar to Schnyder’s dystrophy (SCD) in humans. Chronic corneal fibrosis is one of the leading causes of visual impairment in veterinary ophthalmology. Similar to the situation in human ophthalmology, there is a shortage of corneal donor tissue. Therefore, the overall aim was first to investigate whether corneal stromal stem cells exist in the canine cornea., The second aim was to determine the potential of deriving an in vitro source of corneal stroma cells from corneal stromal stem cells, adipose derived mesenchymal stromal cells (adMSC) and canine induced pluripotent stem cells (ciPSC), to provide a resource for studies investigating the pathogenesis of inherited stromal dystrophies, and for the development of novel cell-based therapies for dogs. First, a canine corneal stromal cell (CSC) population was characterised that demonstrated mesenchymal stromal cell properties, they differentiated into keratocyte-like cells (KDCs) in vitro and appeared to be immune privileged. Second, canine adMSC were differentiated into KDCs, but expressed high levels of a myofibroblastic marker, similar to those found in fibrotic tissue. Third, a modified protocol was established whereby ciPSCs were induced into neural crest (stem) cell lineages and then into KDCs. This led to the successful expression of some keratocyte associated markers in absence of a myofibroblastic expression. Taken together, a novel cell population was characterised in the canine corneal stroma. The differentiation protocols of adMSC and ciPSC led to preliminary results and built a basic foundation for future studies.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Deriving an in vitro source of canine corneal stromal cells for future studies of corneal disease and therapeutic applications
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2022. 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 > 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
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10142821
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