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Title: Role of matrix metalloproteinases in uveoscleral outflow
Author: Molik, Bablin
ISNI:       0000 0004 2750 2166
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2007
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available