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N Hirose, Y Harada, T Nasu, T Tanaka, T Nagata, H Miyamoto, M Oginosawa, A Tawara; Expression of Matrix Metalloproteinases and Tissue Inhibitors of Matalloproteinases in the Monkey Aqueous Outflow Pathway after Prolonged Treatment with Corticosteroid . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1017.
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Purpose: To study the effect of long-term use of corticosteroid on the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in trabecular meshwork and ciliary body. Methods: Repeated doses of triamcinolone acetonide (40mg) were injected subconjunctivally on one eye of 2 macaque monkeys. The contralateral eye was treated with saline and served as control. Each drug was administered 4 times during the period of 6 months before the both eyes were enucleated. The intraocular pressure (IOP) was measured every 2 weeks with applanation tonometer. The tissue was fixed in periodate-lysine-paraformaldehyde and embedded in paraffin. Sections of 3µm thickness were cut and stained by the avidin-biotin complex method with polyclonal antibodies against MMP-2, 3, 9, 10 and TIMP-2, 3 (Santa Cruz Co. Ltd.) for light microscopic immunohistochemistry. Results: Only a weak immunoreactivity for MMPs and TIMPs was detected in the trabecular meshwork of control eyes, whereas repeated periocular triamcinolone treatment exhibited increased expression of TIMP-2. In ciliary muscles, untreated eyes showed moderate staining for MMP-2, 3, 10 and strong reaction for MMP-9. Enhanced expressions of MMP-3, 9 as well as TIMP-2 were observed in response to repository corticosteroid injection. IOP elevation was not confirmed. Conclusion: Our results demonstrate that the administration of corticosteroid with long duration could modulate the expression of MMPs and TIMPs and thereby causing the remodeling of extracellular matrices in trabecular and uveoscleral outflow pathway.
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