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Title: Studies into endothelial cell migration in corneal models : towards application of ROCK inhibitor in treatment
Author: Akhbanbetova, Alina
ISNI:       0000 0004 7962 1343
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2018
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A clear cornea comprising the front surface of the eye is essential for normal vision. In part, a single layer of corneal endothelial cells located on the inner surface of the cornea helps regulate corneal transparency. In corneal endothelial dysfunctions such as Fuchs' endothelial corneal dystrophy (FECD), however, deteriorating endothelial cells lead to corneal cloudiness and a progressive loss of vision. FECD is currently treated via corneal replacement surgeries, which generally are successful but are associated with some potentially problematic issues, including donor shortage and graft rejections. Thus, there is a pressing need for new, less-invasive medical treatments for corneal endothelial dysfunction and the resultant loss of vision. Recently, there has been a growing interest in selective inhibitors of a Rho-associated kinase (ROCK) as agents that can help dysfunctional endothelial cells recover. The research described in this thesis has as its main focus an investigation of new treatment options for corneal endothelial diseases such as FECD. As a baseline, corneal endothelial development is studied because some biological processes in corneal healing have been reported to recapitulate those in corneal embryogenesis. Following this, an assessment is made of the human corneal endothelium and the morphologic changes that occur in FECD. Next, to judge potential new therapeutic approaches to treat vision loss caused by corneal endothelial dysfunction, experiments to assess the potential of transcoreal freezing were conducted. These identified the optimal use of a newly designed cryoprobe and its application for transcorneal freezing to reproducibly damage corneal endothelial cells that line the inner aspect of the cornea. Ingress into the cornea of dyes and medicinal agents was also tested. The concept of this approach is to eliminate the diseased corneal endothelial cells, prior to the medicinal encouragement of more peripheral corneal endothelial cells to regenerate the ablated area. Current research in many laboratories indicates that inhibitors of the Rho kinase pathway within cells lead to them becoming more fibroblast-like in their phenotype, accelerating the migration and inhibit cell death encouraging the endothelial wound healing. This study suggests that a less invasive transcorneal freezing using a 3.4 mm-diameter cryoprobe can be used for reproducible and targeted endothelial cell destruction to be followed by selective ROCK inhibitor application to treat corneal endothelial pathologies such as FECD and potentially other corneal endothelial dysfunctions.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RE Ophthalmology