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Editors Selection IGR 10-4

Basic research: Trabecular meshwork: Remodelling of ECM in POAG and exfoliation syndrome

Zaher Sbeity
Robert Ritch

Comment by Zaher Sbeity & Robert Ritch on:

18199 Matrix metalloproteinases and their inhibitors in the chamber angle of normal eyes and patients with primary open-angle glaucoma and exfoliation glaucoma, Rönkkö S; Rekonen P; Kaarniranta K et al., Graefe's Archive for Clinical and Experimental Ophthalmology, 2007; 245: 697-704


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Matrix metalloproteinases (MMP) and their tissue inhibitors (TIMPs) play a role in extracellular matrix (ECM) remodeling of the trabecular meshwork (TM) and in regulating its outflow facility. It has been suggested that an imbalance of MMPs and TIMPS may play a role in the pathogenesis of glaucoma. The expression of various MMPs and their TIMPs in the aqueous humor may be altered in at least some glaucomas. Schlötzer-Shrehardt et al. (Schlötzer-Shrehardt et al., 2003) suggested that complex changes in the aqueous MMP-TIMP balance and reduced MMP activity may promote abnormal ECM accumulation, characteristic of exfoliation syndrome (XFS), and may be involved in the pathogenesis of both XFG and POAG. MMPs inhibitors, especially TIMP-2, were significantly elevated in the aqueous humor of POAG and XFS eyes compared to cataract eyes (Määttä et al., 2005). In another study, TIMP-1 and connective tissue growth factor levels were elevated in the aqueous of eyes with XFS compared to normal eyes. (Ho et al., 2005). Uveitic glaucoma was reported recently to contain increased expression of MMP-2 and TIMP-2 and their active forms in the aqueous humor when compared with POAG and cataract eyes, possibly reflecting inflammatory disease activity (Määttä et al., 2006).

In this prospective case control study, Rönkkö et al. (418) investigated the expression of MMPs and TIMPs in the chamber angle of normal (n = 8), primary open angle glaucoma (n = 6), and exfoliative glaucoma eyes (n = 5) using immunohistochemical analysis. Six glaucomatous eyes had a minimum of one argon laser trabeculoplasty (ALT). They found significant differences in the levels of MMPs and TIMPs in TM between POAG and XGF eyes. TIMP-3 and TIMP-1 were mostly involved in inhibition of all MMPs in TM of POAG eyes, while TIMP-3 alone was the main MMP-inhibitor in XFG eyes.

A complex MMP-TIMP balance plays a role in ECM remodeling and consequently in the pathogenesis of glaucoma
This study, despite the small number of the subjects analyzed, provides new information about the expression of MMPs and TIMPS at the level of TM and juxtacanalicular tissue. The decreased levels of MMPs in TM did not correlate with published data on MMPs in the aqueous humor,where MMP-2 and MMP-3 has been shown to be increased in both POAG and XFG eyes. Rönkkö et al. Observed no correlation between prostaglandin analogs and the levels of MMPs was observed in POAG and XFG eyes. In the literature, latanoprost was shown to induce MMP-1 in human non-pigmented ciliary epithelial cells (Hinz et al. 2005).

Konstas et al. Also reported elevated MMPs in the aqueous of patients with XFG and on latanoprost compared to XFG patients not on latanoprost. It would be also interesting to know if the control eyes were age matched or not as we do not know what happens to MMP/TIMP balance with age. Also, the authors did not mention if there was a difference in MMP/TIMP balance between eyes which had undergone ALT and the untreated ones.

A complex MMP-TIMP balance plays a role in ECM remodeling and consequently in the pathogenesis of glaucoma. Various factors, such as trabecular or inflammatory cells, interleukins, prostaglandin analogs, and ALT may influence the production and metabolism of MMPs. Further studies are needed to enable us to better understand the exact expressions and pattern of MMP-TIMP balance in different glaucomas.

References

  1. Schloetzer-Schrehardt XX, et al. Matrix metalloproteinases and their inhibitors in aqueous humor of patients with pseudoexfoliation syndrome/glaucoma and primary open-angle glaucoma. IOVS 2003; 44: 1117-25.
  2. Ho XX, et al. Elevated aqueous humor tissue inhibitor of matrix metalloproteinase-1 and connective tissue growth factor in pseudoexfoliation syndrome. Br J Ophthalmol 2005; 89: 169-73.
  3. Konstas XX, et al. Latanoprost therapy reduces the levels of TGF beta 1 and gelatinases in the aqueous humor of patients with exfoliative glaucoma. Exp Eye Res 2006; 82: 319-22.
  4. Määttä XX, et al. Levels and activation of matrix metalloproteinases in aqueous humor are elevated in uveitis-related secondary glaucoma. J Glaucoma 2006; 15: 229-37.
  5. Määttä XX, et al. Matrix metalloproteinases and their tissue inhibitors in aqueous humor of patients with primary open-angle glaucoma,exfoliation syndrome, and exfoliation glaucoma. J Glaucoma 2005; 14: 64-9.
  6. Hinz XX, et al. Latanoprost induces matrix metalloproteinase-1 expression in human non-pigmented ciliary epithelial cells through a cycloxgenase-2-dependent mechanism. FASEB J 2005; 19: 1929-31.
     

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