Abstract
BackgroundTo quantify the levels of tissue inhibitor of metalloproteinase 4 (TIMP4) and its ratios with free metalloproteinases (MMP) in the aqueous humor of patients with primary open angle glaucoma (POAG), pseudoexfoliation syndrome (PXS) and pseudoexfoliative glaucoma (PXG) and to evaluate a possible imbalance between MMPs and TIMPs in these samples.MethodsFree MMP2, MMP3, MMP9, TIMP1, TIMP2, TIMP4 concentrations and active levels of MMP2 and MMP3 were determined with immunoassay ELISA and activity assay kits in 168 aqueous samples.ResultsTIMP4 was elevated in glaucoma patients(POAG: 0.95 ± 0.49 PXG: 1.28 ± 1.38 pg/ml. p < 0.001). POAG, PXS and PXG samples demonstrated higher MMP2, TIMP1 and TIMP2 concentrations (p < 0.001). Samples from the PXS and PXG groups had a lower total/active MMP2 ratio (p < 0.004 and p < 0.008 respectively). Stoichiometric analysis showed an overbalance of TIMPsover MMPs in both POAG & PXG groups,especially of TIMP4.ConclusionTIMP4 elevation is a novel finding in glaucomatous eyes. A disregulation of extracellular matrix homeostasis is suggested in POAG, PXS and PXG.
Highlights
To quantify the levels of tissue inhibitor of metalloproteinase 4 (TIMP4) and its ratios with free metalloproteinases (MMP) in the aqueous humor of patients with primary open angle glaucoma (POAG), pseudoexfoliation syndrome (PXS) and pseudoexfoliative glaucoma (PXG) and to evaluate a possible imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) in these samples
TIMP4 levels TIMP4 levels were higher in both glaucoma groups (POAG and PXG) when compared to controls (p = 0.001)
In the PXS group, TIMP4 concentrations presented no statistical difference from controls (p = 0.936) (Table 3)
Summary
To quantify the levels of tissue inhibitor of metalloproteinase 4 (TIMP4) and its ratios with free metalloproteinases (MMP) in the aqueous humor of patients with primary open angle glaucoma (POAG), pseudoexfoliation syndrome (PXS) and pseudoexfoliative glaucoma (PXG) and to evaluate a possible imbalance between MMPs and TIMPs in these samples. The normal architecture and function of the juxtacanalicular TM is altered by the pathological accumulation of connective tissue and the partial loss of endothelial cells [5,6]. Other local factors such as the expression of vasoconstrictive molecules and oxidative stress may be involved [7,8]. The pseudoexfoliative material might congest the outflow pathways of the TM contributing to the elevation of the IOP and may be involved in the development of pseudoexfoliative glaucoma (PXG) [9,10]
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