Rönkkö Seppo, Rekonen Petri, Kaarniranta Kai, Puustjärvi Tuomo, Teräsvirta Markku, Uusitalo Hannu
Department of Ophthalmology, University of Kuopio, 70211, Kuopio, Finland.
Graefes Arch Clin Exp Ophthalmol. 2007 May;245(5):697-704. doi: 10.1007/s00417-006-0440-1. Epub 2006 Oct 7.
In glaucoma, extensive pathological changes occur in the trabecular meshwork (TM) and juxtacanalicular tissue of the chamber angle. Aqueous humor drainage is disturbed due to the accumulation of extracellular matrix (ECM) material in the outflow system. Matrix metalloproteinases (MMPs) remodel ECM material and, thus, they may have a role in regulating outflow facility and intraocular pressure (IOP). This study examined the expression of MMPs and tissue inhibitors of MMPs (TIMPs) in the chamber angle of normal eyes and in primary open-angle glaucoma (POAG) and in exfoliation glaucoma (ExG).
TM tissues were isolated from healthy donor eyes for corneal transplantation. Specimens of the inner wall of Schlemm's canal and the juxtacanalicular tissue were collected from patients with POAG or ExG during deep sclerectomy operation. Monoclonal antibodies against MMPs (MMP-1, -2, -3, and -9) and antibodies against TIMPs (TIMP-1, -2, and -3) were used for immunohistochemical staining.
Immunoreactivity for MMP-2, TIMP-2, or TIMP-3 was observed in human normal TM and in the inner wall of Schlemm's canal. In general, immunoreactions for all of the tested MMPs were more intense in POAG samples than in ExG samples or in the control group. The only exception was the MMP-2 level, which was the highest in the control group. The staining intensity of MMP-1 or MMP-3 was significantly higher in POAG when compared to ExG. TIMP-1 was significantly increased in POAG compared with ExG and there were no marked differences in the levels of TIMP-2 or TIMP-3 between POAG and ExG. The ratios of MMP-1/TIMP-1 and MMP(1+2+3+9) and TIMP(1+2+3) were significantly higher in samples from POAG compared to those of ExG.
Our results reveal an expression imbalance between MMPs and their endogenous tissue inhibitors in tissue samples from patients with POAG and ExG. Differences in immunohistochemical reactions reflect discrete local pathogenic mechanisms involved in POAG and ExG. With respect to the proposed role of MMPs in the remodeling of ECM material, this may point to a weaker reactivity to the accumulation of ECM material in TM in ExG than POAG eyes.
在青光眼患者中，小梁网（TM）和房角的邻管组织会发生广泛的病理变化。由于流出系统中细胞外基质（ECM）物质的积累，房水引流受到干扰。基质金属蛋白酶（MMPs）可重塑ECM物质，因此它们可能在调节房水流出率和眼压（IOP）方面发挥作用。本研究检测了正常眼、原发性开角型青光眼（POAG）和剥脱性青光眼（ExG）房角中MMPs及其组织抑制剂（TIMPs）的表达情况。
从健康供体眼分离TM组织用于角膜移植。在深层巩膜切除术期间，从POAG或ExG患者中收集施莱姆管内壁和邻管组织的标本。使用抗MMPs的单克隆抗体（MMP-1、-2、-3和-9）和抗TIMPs的抗体（TIMP-1、-2和-3）进行免疫组织化学染色。
在人正常TM和施莱姆管内壁中观察到MMP-2、TIMP-2或TIMP-3的免疫反应性。一般来说，所有检测的MMPs在POAG样本中的免疫反应比在ExG样本或对照组中更强烈。唯一的例外是MMP-2水平，其在对照组中最高。与ExG相比，POAG中MMP-1或MMP-3的染色强度显著更高。与ExG相比，POAG中TIMP-1显著增加，POAG和ExG之间TIMP-2或TIMP-3水平无明显差异。与ExG样本相比，POAG样本中MMP-1/TIMP-1以及MMP（1+2+3+9）与TIMP（1+2+3）的比值显著更高。
我们的结果揭示了POAG和ExG患者组织样本中MMPs与其内源性组织抑制剂之间的表达失衡。免疫组织化学反应的差异反映了POAG和ExG中不同的局部致病机制。就MMPs在ECM物质重塑中的作用而言，这可能表明ExG眼中TM对ECM物质积累的反应性比POAG眼弱。
