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