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Immunoregulation of acquired ocular immunobullous disease

Williams, Geraint P. (2012)
Ph.D. thesis, University of Birmingham.

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Ocular Mucous Membrane Pemphigoid (OcMMP) is a blinding immunobullous disease, characterised by auto-antibody driven conjunctival inflammation and scarring. My hypothesis was that progressive fibrosis in OcMMP, occurring in the apparent absence of clinical inflammation, was driven by underlying inflammatory processes.

I observed that in OcMMP, progressive scarring did occur in the apparent absence of clinically identifiable inflammation and I was able to improve clinical documentation by developing and validating an objective Fornix Depth Measurer (FDM) for assessment of scarring.

I optimised non-invasive Ocular Surface Impression Cytology (OSIC) combined with flow cytometry to characterise conjunctival leukocytes. I found that CD8αβ+ effector memory, cytotoxic, mucosal-homing T cells were the dominant population in health. This population was unaltered with age but CD4+ T cells, capable of producing IFN-γ, increased.

In OcMMP, the conjunctiva was characterised by decreased CD8+ lymphocytes and an elevation in CD45INTCD11b+CD16+CD14- neutrophils. Although neutrophils correlated with clinical inflammation, they were even present in the absence of identifiable conjunctivitis. This elevation was associated with progression of scarring assessed by FDM, even in the clinically Non-inflamed eye.

These findings confirmed my hypothesis and provide a platform for quantifying neutrophils as a biomarker of sub-clinical inflammation and their role in the scarring process.

Type of Work:Ph.D. thesis.
Supervisor(s):Rauz, Saaeha and Curnow, SJ
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Immunity and Infection
Additional Information:

Publications in the Appendix are available at

Subjects:RE Ophthalmology
Institution:University of Birmingham
ID Code:3235
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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