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Correlation Of Matrix Metalloproteinase And Matrix Metalloproteinase Inhibitor With Glaucoma

Posted on:2006-02-07Degree:DoctorType:Dissertation
Country:ChinaCandidate:J Q ShenFull Text:PDF
GTID:1104360155466215Subject:Ophthalmology
Abstract/Summary:PDF Full Text Request
PURPOSE: To determine whether application of a broad-spectrum matrix metalloproteinase (MMP) inhibitor, GM6001, could reduce scarring after glaucoma filtration surgery.METHODS: In a randomized, prospective, masked-observer study, 24 New Zealand White rabbits underwent glaucoma filtration surgery. The animals were randomly allocated to 4 groups, 3 receive GM6001 cotton swab of 3000μM, 2000μM, 1000μM for 5 minutes, respectively, and 1 receive nothing during the operation. The animals were killed on days 30. Clinical characteristics, which included bleb morphology and intraocular pressure, were recorded. Tissue sections were HE stainedRESULTS: The presence of bleb was significantly prolonged in the GM6001-treated group compared with the control group(P < 0.001). The blebs had survived to day average 30 (28-32),in the GM6001-treated groupA(3000μM); the bleb of GM6001-treated group B survived to average 26.5(24-28); for GM6001-treated group C, the bleb suevived to average 21.5(14-24),whereas no blebs survived to day 15 (average 11) for the control group . The intraocular pressure remainedsignificantly lower throughout the course of the experiment in the GM6001 group compared with the control group (P < 0.001). Histologically, less scar tissue was observed at the trabeculectomy site with inhibition of MMP, compared with control group.CONCLUSIONS: This study suggested that the healing response after surgery can be modulated by inhibiting effects of MMPs. Inhibition of MMP significantly improved 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.Objective : To determine the expression and distribution of matrix metalloproteinase(MMP-l,2,3,7,9) and their tissue inhibitors of metalloprotein-ases(TIMP-l,2,3,4)in normal human iris, ciliary body, choroid , retina pigmentary epithelium.Methods: . Immunofluorescent SABC-Cy3 method was used to investigate the expression of MMP-1,2,3,7,9 and TIMP-1,2,3,4 in iris, ciliary body, choroid and RPE from normal human eyes.Results: l.In the iris, staining intensity generally followed this pattern: anterior border>anterior epithelium>iris stroma>posterior epithelium. In anterior border, staining for MMP-1,2,3 and TIMP-1 was stronger than that of MMP-7,9 and TIMP-2,3,4; in anterior epithelium, staining for MMP-2 was heavier than that of other antibodies; in the stroma and posterior epithetlium all staining was slight.2. In the ciliary body, the patterns of intensity of the staining was non-pigmentepithelium >ciliary muscle >pigment epithelium >stroma for all antibodies. In the non-pigmentepithelium, pigment epithelium and stroma the staining for MMP-1,2,3 and TIMP-3 was heavier than that for MMP-3,7,9 and TIMP-1,2,4, but in the ciliary muscle MMP-2 and TIMP-2,3 staining was stronger than other staining. Whereas staining for MMP-1,2,3,7,9 and TIMP-1,2,4 was mainly in the cytoplasm of both non-pigment epithelium and pigment epithelium cells.staining for TIMP-3 was mostly in the basement membrane of the epithelium.3. In the choroid, all saining was moderately strong, but the staining for MMP-1,2 and TIMP-1 was sligtly stronger than that for other antibodies.4. The staining for MMP-1,2,3,7,9 and TIMP-1,2,3,4 was seen in the RPE. In the RPE, the staining for MMP-1,2,3,7,9 and TIMP-1,2,3,4 was all apparent.Conclusions: In normal eyes, staining for MMP-1,2,3,7,9 and TIMP-1,2,3,4 was observed in the iris, ciliary body, choroid , retina pigmentary epithelium, although there was marked variation in the intensity of staining in different regions. And there are certain expression patterns in some parts.Objective : To determine the expression and distribution of matrix metalloproteinase(MMP-l,2,3,7,9) and their tissue inhibitors of metal loprotein-ases(TIMP-l,2,3,4)in normal human retina and optic nerve .Methods: Immunohistochemical SP method was employed to detect the expression and distribution of MMP-1,2,3,7,9 and TIMP-1,2,3,4 in, retina, optic nerve from normal human eyes.Results: The staining for MMP-1,2,3,7,9 and TIMP-1,2,3,4 was seen in the neurosensory retina . In the neurosensory retina, the staining for MMP-1,2,3 and TIMP-1,2,3,4 was strong and there was differences in the staining intensity for these seven antibodies; the staining for MMP-7 and MMP-9 was observeved mostly in the ganglion cells and rod and cone, but the former was strong and the latter was very slight. For MMP-7 ,the stainig in outer segment was stronger than that in inner segment, while for other MMPs and TIMPs, the staining in inner segment was stronger than that in outer segment.In the optic nerve, apparent staining was observed mostly in the nerve fibers and glial cells. In the nerve fibers, staining for MMP-1 was strong, stainig for MMP-2 and TIMP-1,2,3,4 was slight ,and staining for MMP-3,7,9 was the slightest. And in the cytoplasme of glial cells ,staining for MMP-1,3 was the strongest, for MMP-2 and TIMP-1,2,3,4 was slight, for MMP-9 was the slightest and for MMP-7 was unseen.Conclusions: In normal eyes, staining for MMP-1,2,3,7,9 and TIMP-1,2,3,4 wasobserved in the retina, optic nerve without obvious specificity , although there was marked variation in the intensity of staining in different regions. And there are certain expression patterns in some parts.
Keywords/Search Tags:Matrix metalloproteinases, Tissue inhibitors of metallopro-teinases, Extracellular matrix, Immumohistochemistry, Immunofluorescent, Matrix Metalloproteinase, Matrix Metalloproteinase Inhibitor, Immunohistochenstry, Extracellular matrix, ECM
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