Models to investigate the role of anti-transforming growth factor beta antibodies in lens and corneal wound healing.
Doctoral thesis, UCL (University College London).
The eye is a unique structure and needs to maintain transparency along its visual axis for good quality vision. The lens and cornea are vital transparent structures in the visual axis and are susceptible to scarring following the trauma of surgery. The aim of this thesis was to establish models to observe wound healing in the lens and cornea and investigate the role of transforming growth factor beta (TGF\beta) and its antibodies on the scarring process. In this thesis a system of high resolution imaging in the rabbit was established visualising down to the level of individual lens epithelial cells (LECs) in-vivo. Four phases of posterior capsular opacification (PCO) were characterised using the model. An initial proliferation of LECs in the first two weeks is followed by a week of regression. A plateau phase of two weeks represents no major changes on the posterior capsule but ongoing equatorial proliferation. Finally a wave of proliferating LECs marched in from the periphery to cover the posterior capsule. This process was consistent and could be quantified and analysed for use in translational research. The effect of anti TGF-\beta2 antibodies delivered at the time of surgery was to increase the proliferation of lens epithelial cells in the initial period with no toxic effects. Also in this thesis a model of corneal organ culture was established to allow quantification of epithelial and stromal wound healing. Scanning laser confocal microscopy was used to quantify stromal changes which correlated well with histology scores for scarring indicating the changes seen on confocal microscopy represent a real change in corneal stroma. Treatment with TGF\beta1 antibody did not promote or inhibit epithelial healing. However, it significantly reduced stromal scarring after epithelial scrape wound. The trend towards reduced stromal scarring after lamellar keratectomy did not reach significance after TGF\beta1 antibody treatment The models developed and validated in this thesis may be useful in evaluating new treatment modalities in translational research and aid in their progress to clinical applicability.
|Title:||Models to investigate the role of anti-transforming growth factor beta antibodies in lens and corneal wound healing|
|Additional information:||Authorisation for digitisation not received. The abstract contains LaTex text, please see thesis for rendered equations|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology|
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