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The role of transforming growth factor-β (TGF-β) in the conjunctival scarring process following glaucoma surgery

Cordeiro, Maria Francesca; (1998) The role of transforming growth factor-β (TGF-β) in the conjunctival scarring process following glaucoma surgery. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Excessive scarring is a major cause of morbidity in clinical medicine and ophthalmology. Currently available anti-scarring agents such as mitomycin-c (MMC) are associated with severe complications. The aim of this thesis was to investigate the actions of Transforming Growth Factor-β (TGF-β) in the conjunctival scarring process following glaucoma filtration surgery with a view to defining its role and efficacy as an alternative and safer anti-scarring strategy. The three human isoforms of TGF-β were investigated with several in vitro and in vivo experimental models of conjunctival healing. All isoforms were shown to behave similarly to each other in stimulating the conjunctival scarring response in a concentration-dependent manner, and their cellular effects appeared to depend on the surrounding extracellular environment. All three isoforms were expressed during normal conjunctival healing in vivo, with TGF-β2 exhibiting greatest activity. Exogenous administration of TGF-β2 was found to effectively reverse the anti-scarring effects of subconjunctival MMC. A new TGF-β2 antibody, assessed during the project, demonstrated effective antagonism of TGF-β2 fibroblast-mediated conjunctival scarring activity. A clinical trial of this antibody is planned to commence at Moorfields Eye Hospital in 1998, for assessing its potential use as a therapeutic anti-scarring agent in glaucoma filtration surgery. This work has shown TGF-β to be a potent modulator of the conjunctival wound healing response. Although my studies suggest a clinical application of TGF-β2 and its neutralisation in reducing ocular scarring, development of TGF-β-related therapies in the eye may have widespread implications for use throughout medicine.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The role of transforming growth factor-β (TGF-β) in the conjunctival scarring process following glaucoma surgery
Language: English
Additional information: This thesis has been digitised by ProQuest.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
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/44741
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