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TT L Wong, JT Daniels, AL Mead, G Murphy, PT Khaw; Inhibition of Matrix Metalloproteinases Reduces Scarring Following Experimental Glaucoma Filtration Surgery . Invest. Ophthalmol. Vis. Sci. 2002;43(13):870.
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Purpose: Matrix metalloproteinases (MMPs) are a group of proteolytic enzymes important in wound healing. In this study we set out to determine whether the post-operative application of a broad-spectrum MMP inhibitor (Galardin) could reduce scarring following glaucoma filtration surgery. Methods: In a randomised, masked-observer study, 40 New Zealand white rabbits underwent modified glaucoma filtration surgery. The animals were randomly allocated to receive post-operative subconjunctival injections of either phosphate buffered saline (PBS) or 100uM Galardin by a masked individual for 10 consecutive days. The animals were sacrificed on days 7, 14, 21 and 30. Clinical characteristics which included bleb morphology, intraocular pressure and anterior chamber activity were recorded. Tissue sections were immunohistochemically stained for alpha smooth muscle actin (ASMA) and extracellular matrix components in both the control and treated eyes. Results: Mean bleb survival was very significantly prolonged in the Galardin group (28.5 days) compared to the control group (18.5 days). The intraocular pressure remained significantly lower throughout the course of the experiment in the treated group compared to the control (p<0.0017). Histologically, less scar tissue was observed at the sclerostomy site in the Galardin group compared to the control. These results were equivalent to the effects seen previously with mitomycin-C treatment, without the associated tissue damage. Conclusion: The data presented suggests that the healing response following surgery can be modulated by inhibiting the effects of MMPs. An MMP inhibitor was shown to very significantly improve surgical outcome by reducing the amount of scar tissue produced. By targeting the actions of these proteolytic enzymes, a more controlled and physiological method of modulating scarring may be achieved.
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