Matrix metalloproteinases and tissue inhibitors of metalloproteinases in the aqueous humour of patients with primary angle closure glaucoma - a quantitative study

Abstract

BackgroundAltered levels of specific matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the aqueous humour of primary open-angle glaucoma (POAG) eyes have been described. In this study, levels of specific MMPs and TIMPs in the aqueous humour of primary angle-closure glaucoma (PACG) eyes were measured and compared with those of POAG as well as non-glaucoma control eyes.MethodsAqueous humour from 16 PACG, 28 POAG and 27 control eyes were sampled during intraocular surgery. Levels of total protein, MMP-2, MMP-3, TIMP-1 and TIMP-2 were quantified by protein assay and enzyme immunoassay.ResultsTotal protein levels were significantly higher in PACG (0.426 ± 0.126 mg/ml, p = 0.043) and POAG (0.578 ± 0.360 mg/ml, p = 0.007) compared to controls (0.292 ± 0.192 mg/ml). The difference between PACG and POAG was not significant (p = 0.158). MMP-2 was significantly higher in PACG (p = 0.032) and POAG (p < 0.001) compared to controls. The difference between PACG and POAG was also not significant (p = 0.133). MMP-3 was significantly higher in POAG compared to controls (p = 0.002) and PACG (p = 0.029). The difference between PACG and controls was not significant (p = 0.962). TIMP-1 was significantly higher in PACG (p = 0.049) and POAG (p = 0.010) compared to controls. The difference between PACG and POAG was also not significant (p = 0.961). TIMP-2 was significantly higher in POAG (p = 0.004) compared to controls. The difference between PACG and either controls or POAG was not significant (p > 0.05). Although not statistically significant (p > 0.05), the MMP-2/TIMP-2 ratio was highest in PACG (2.83 ± 7.40), followed by POAG (1.38 ± 1.55) and controls (1.34 ± 3.05). Similarly, the MMP-2/TIMP-1 ratio was highest in PACG (1.50 ± 1.69), followed by POAG (1.40 ± 0.77) and controls (1.15 ± 0.92). The MMP-2 + MMP-3/TIMP-1 + TIMP-2 ratio was higher in PACG (0.83 ± 0.80) and POAG (0.82 ± 0.53) compared to controls (0.70 ± 0.63). In both POAG and PACG, there were no significant differences in the levels of total protein, MMP-2, MMP-3, TIMP-1 and TIMP-2 between patients on prostaglandin analogues and those not.ConclusionWe found altered levels of MMPs and TIMPs as well as imbalance of MMP:TIMP ratios in the aqueous humour of PACG eyes that were different from POAG and non-glaucoma control eyes.

Lowered Decorin With Aberrant Extracellular Matrix Remodeling in Aqueous Humor and Tenon's Tissue From Primary Glaucoma Patients

“…The estimated sample size for the study was calculated from the mean total protein in controls (0.292 6 0.192), POAG (0.578 6 0.360), and PACG (0.426 6 0.126) mg/mL as mentioned in the reference study 27 with a significance level of 5%, power of 90%, and the effect size of 0.27 using G * Power 3.1 software, and was found to be minimum of 44 in each group.…”

Myocilin Regulates Metalloprotease 2 Activity Through Interaction With TIMP3

“…58 , 59 The upregulation of several MMP mRNAs including MMP2 mRNA has been reported in a steroid-induced mouse glaucoma model, 60 and MMP2 was also moderately increased in the TM and aqueous humor of patients with POAG as compared with healthy individuals. 48 , 61 , 62 Furthermore, changes in the balance between proteases and protease inhibitors (TIMP3) may modify choroid thickness. 63 A decrease in choroid thickness is associated with a number of eye disorders including myopia and AMD.…”

The SPARC-related modular calcium binding protein 2 (<em>SMOC2</em>) gene polymorphism in primary glaucoma: a case-control study

“…SMOC2 with multiple domains has the potential to act as protease inhibitors 39. The protease/antiprotease imbalance has also been reported as a key factor in abnormal matrix accumulation leading to potential involvement in the pathogenesis of glaucoma 40. It can be suggested that polymorphism in the SMOC2 gene may be associated with low levels of protease inhibitor subsequently resulting in high MMPs.…”