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Role of matrix metalloproteinases in uveoscleral outflow

Molik, Bablin 2007. Role of matrix metalloproteinases in uveoscleral outflow. PhD Thesis, Cardiff University.

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Abstract

Prostaglandin derivatives form the most widely used medicinal treatments given to glaucoma patients to lower intraocular pressure. Prostaglandins are believed to increase matrix metalloproteinase (MMP) and tissue inhibitor of matrix metalloproteinase (TIMP) activity, leading to increased in aqueous outflow, via uveoscleral outflow pathway. However, the direct impact of MMPs on the tissues within uveoscleral pathway has not been determined. The aim of this project was to compare the direct effect of prostaglandins and MMPs on the tissues within the uveoscleral outflow pathway. To determine the effect of known inducers of MMP activity, scleral fibroblasts and ciliary muscle cells were cultured in the presence of interleukin-1a, tumour necrosis factor, transforming growth factor p and prostaglandin F2a (PGF2a). The effect of prostaglandin F2a and MMPs on the uveoscleral pathway tissue i.e. sclera, was assessed as a measure of permeability, molecular and supramolecular scleral collagen integrity and proteoglycan composition. A significant induction of MMP 1, 2, 3 and 9 secretion and activity with cytokines and PGF2a, within human scleral fibroblast and ciliary muscle cell cultures (p<0.05). A 3-fold increase in scleral permeability was observed within 24 hour of incubation in PGF2a, whereas upto 10-fold increase was observed in MMP treated. The helical rise per residue (at 1.5nm), lateral packing (at 0.29nm) and D-spacing (at 66nm) of scleral collagen was unaffected by MMP and PGF2a incubation. Significant change in aggrecan degradation was observed within scleral tissue incubated in MMP and PGF2a (p<0.05). However, no significant change in small leucine rich proteoglycans i.e. biglycan, decorin and lumican, within sclera occurred within sclera incubated in MMP or PGF2a.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Optometry and Vision Sciences
Subjects: R Medicine > RE Ophthalmology
ISBN: 9781303209543
Date of First Compliant Deposit: 30 March 2016
Last Modified: 25 Oct 2017 14:27
URI: https://orca.cardiff.ac.uk/id/eprint/54613

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