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T. Sherwin, N.H. Brookes, I.P. Loh; Epithelial, Keratocyte and Nerve Interactions in Keratoconic Corneas . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4961.
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PURPOSE: Keratoconus is a debilitating corneal ectasia that is the leading presenting need for corneal grafting. This study aims to 1. Examine the role of the corneal nerves in providing a route across Bowman’s layer for destructive interactions between the epithelium and the stroma. 2. Examine and quantify the extent and position of nerve hypertrophy 3. Correlate these findings to elucidate the cause of nerve hypertrophy and propose cellular mechanisms behind the progression of keratoconus. METHODS: Sections from keratoconic buttons were labelled with cell and nerve fibre specific probes prior to labelling with antibodies to catabolic enzymes cathepsins B and G, and neurotrophic factors. The resulting multi–channel labelled tissue samples were then examined by confocal microscopy and quantitatively analysed. The corneal volumes were analysed as ten percentile portions radiating out from the centre of the cone, with the thinnest part of the recipient button designated as 0% and the most peripheral (most ‘normal’) region designated as 100%. RESULTS:There was a high degree of correlation between cellular perturbations of Bowman’s layer and sites of nerve passage. In addition, these sites were rich in cathepsin B and G labelling, indicating substantial cellular and extra–cellular matrix breakdown. Nerve fibre thickenings found in the 70–89% and 20–39% corneal thickness regions were significantly larger in cross sectional area and volume than those found at the periphery of the cone or the published values for normal corneal nerves. Hypertrophic nerves were significantly further from Bowman’s membrane in the 50–59% region. Investigations into whether these phenomena are contributing to the disease progression or merely an effect are continuing. Initial results suggest that neurotrophic factors may be involved in the continuing deterioration of these compromised areas of keratoconic corneas. CONCLUSIONS:This study combined with previous work has led us to erect a model of keratoconic progression via continuous feedback looping of an aberrant repair mechanism in which the interactions between keratocytes, nerve fibres and epithelial cells are destructive and uncoordinated.
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