Matrix metalloproteinases and their inhibitors in aqueous humor of patients with pseudoexfoliation syndrome/glaucoma and primary open-angle glaucoma
Matrix metalloproteinases and their inhibitors in aqueous humor of patients with pseudoexfoliation syndrome/glaucoma and primary open-angle glaucoma
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DOI：
10.1167/iovs.02-0365
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发表时间：
2003-03-01
影响因子：
4.4
通讯作者：
Naumann, GOH
中科院分区：
文献类型：
--
作者：
Schlötzer-Schrehardt, U;Lommatzsch, J;Naumann, GOH
目的。目的：测定假表皮脱落（PEX）综合征、PEX型青光眼（PEX）、原发性开角型青光眼（POAG）和白内障患者房水和血清样品中基质金属蛋白酶（MMPs）及其内源性抑制剂（TIMPs）的存在、活性和数量差异。分别采集100例PEX综合征、PEX型青光眼、POAG和白内障患者的房水和血清样本。通过酶谱分析、Western blot分析和特异性免疫测定测定MMP-1、-2、-3、-7、-9和-12以及TIMP-1和-2的水平。活性测定试剂盒用于定量内源性活化的MMP-2和-9的水平。MMP-2、-3、-7、-9和-12以及TIMP-1和-2在所有组患者的房水样品中被鉴定出，timp的摩尔含量超过MMPs的6至7倍。尽管血清样品无显著差异，但与白内障眼相比，伴青光眼和不伴青光眼的PEX眼的水样中总MMP-2和-3以及TIMP-1和-2的浓度明显更高。POAG眼水样中MMP-2、-3和timp - 1的含量也较高，但差异不显著。然而，内源性活化的MMP-2水平在PEX和POAG样品中均显著降低。在白内障样本中，MMP-2与其主要抑制剂TIMP-2的比例是平衡的，但在PEXG患者的样本中，比例降低，导致TIMP-2高于MMP-2。研究结果提示，房水中局部MMP- timp平衡的复杂变化和MMP活性的降低可能促进PEX综合征的异常基质积累特征，并可能与PEX型青光眼和POAG的发病机制有关。
PURPOSE. To determine the presence, activity, and quantitative differences of matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in aqueous humor and serum samples of patients with pseudoexfoliation (PEX) syndrome, PEX glaucoma (PEXG), primary open-angle glaucoma (POAG), and cataract.METHODS. Aqueous humor and serum, samples were collected from 100 patients with PEX syndrome, PEX glaucoma (PEXG), POAG, and cataract, respectively. Levels of MMP-1, -2, -3, -7, -9, and -12 and TIMP-1 and -2 were determined by zymography, Western blot analysis, and specific immunoassays. Activity assay kits were used to quantitate levels of endogenously activated MMP-2 and -9.RESULTS. MMP-2, -3, -7, -9, and -12 and TIMP-1 and -2 were identified in human aqueous humor samples from all groups of patients with a six to sevenfold molar excess of TIMPs over MMPs. Whereas serum samples showed no significant differences, total MMP-2 and -3 and TIMP-1 and -2 were detected at significantly higher concentrations in aqueous samples from PEX eyes with and without glaucoma compared with cataractous eyes. MMP-2 and -3 and TIMP-I were also detected in higher, but not significantly different, amounts in aqueous samples of POAG eyes. However, levels of endogenously activated MMP-2 were significantly decreased in both PEX and POAG samples. The ratio of MMP-2 to its principal inhibitor TIMP-2 was balanced in cataract samples, but was decreased in samples from patients with PEXG, resulting in an excess of TIMP-2 over MMP-2.CONCLUSIONS. The findings suggest that complex changes in the local MMP-TIMP balance and reduced MMP activity in aqueous humor may promote the abnormal matrix accumulation characteristic of PEX syndrome and may be causally involved in the pathogenesis of both PEX glaucoma and POAG.