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Matrix metalloproteinases and their inhibitors in the chamber angle of normal eyes and patients with primary open-angle glaucoma and exfoliation glaucoma

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Abstract

Background

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).

Methods

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

Results

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 MMP1+2+3+9 and TIMP1+2+3 were significantly higher in samples from POAG compared to those of ExG.

Conclusions

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.

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References

  1. Aasved H (1971) The frequency of optic nerve damage and surgical treatment in chronic simple glaucoma and capsular glaucoma. Acta Ophthalmol 49(4):589–600

    CAS  Google Scholar 

  2. Alexander JP, Samples JR, Van Buskirk EM, Acott TS (1991) Expression of matrix metalloproteinases and inhibitor by human trabecular meshwork. Invest Ophthalmol Vis Sci 32(1):172–180

    PubMed  CAS  Google Scholar 

  3. Coleman AL (1999) Glaucoma. Lancet 354(9192):1803–1810

    Article  PubMed  CAS  Google Scholar 

  4. Forsius H (1979) Prevalence of pseudoexfoliation of the lens in Finns, Lapps, Icelanders, Eskimos, and Russians. Trans Ophthalmol Soc UK 99(2):296–298

    PubMed  CAS  Google Scholar 

  5. Futa R, Shimizu T, Furuyoshi N, Nishiyama M, Hagihara O (1992) Clinical features of capsular glaucoma in comparison with primary open-angle glaucoma in Japan. Acta Ophthalmol 70(2):214–219

    CAS  Google Scholar 

  6. Gross J, Lapiere CM (1962) Collagenolytic activity in amphibian tissues: a tissue culture assay. Proc Natl Acad Sci USA 48:1014–1022

    Article  PubMed  CAS  Google Scholar 

  7. Ho SL, Dogar GF, Wang J, Crean J, Wu QD, Oliver N, Weitz S, Murray A, Cleary PE, O’Brien C (2005) Elevated aqueous humour tissue inhibitor of matrix metalloproteinase-1 and connective tissue growth factor in pseudoexfoliation syndrome. Br J Ophthalmol 89(2):169–173

    Article  PubMed  CAS  Google Scholar 

  8. John A, Tuszynski G (2001) The role of matrix metalloproteinases in tumor angiogenesis and tumor metastasis. Pathol Oncol Res 7(1):14–23

    Article  PubMed  CAS  Google Scholar 

  9. Kerrigan JJ, Mansell JP, Sandy JR (2000) Matrix turnover. J Orthod 27(3):227–233

    PubMed  CAS  Google Scholar 

  10. Konstas AG, Stewart WC, Stroman GA, Sine CS (1997) Clinical presentation and initial treatment patterns in patients with exfoliation glaucoma versus primary open-angle glaucoma. Ophthalmic Surg Lasers 28(2):111–117

    PubMed  CAS  Google Scholar 

  11. Krause U, Helve J, Forsius H (1973) Pseudoexfoliation of the lens capsule and liberation of iris pigment. Acta Ophthalmol (Copenh) 51(1):39–46

    Article  CAS  Google Scholar 

  12. Krause U, Alanko HI, Kärnä J, Miettinen R, Larmi T, Jaanio E, Ollila OI, Takala J (1988) Prevalence of exfoliation syndrome in Finland. Acta Ophthalmol Suppl (Copenh) 66(184):120–122

    Article  Google Scholar 

  13. Lahm A, Uhl M, Lehr HA, Ihling C, Kreuz PC, Haberstroh J (2004) Photoshop-based image analysis of canine articular cartilage after subchondral damage. Arch Orthop Trauma Surg 124(7):431–436

    Article  PubMed  CAS  Google Scholar 

  14. Lehr HA, Mankoff DA, Corwin D, Santeusanio G, Gown AM (1997) Application of photoshop-based image analysis to quantification of hormone receptor expression in breast cancer. J Histochem Cytochem 45(11):1559–1565

    PubMed  CAS  Google Scholar 

  15. Lindblom B, Thorburn W (1982) Prevalence of visual field defects due to capsular and simple glaucoma in Halsingland, Sweden. Acta Ophthalmol (Copenh) 60(3):353–361

    CAS  Google Scholar 

  16. Lindblom B, Thorburn W (1984) Functional damage at diagnosis of primary open angle glaucoma. Acta Ophthalmol (Copenh) 62(2):223–229

    CAS  Google Scholar 

  17. Liotta LA, Tryggvason K, Garbisa S, Robey PG, Abe S (1981) Partial purification and characterization of a neutral protease which cleaves type IV collagen. Biochemistry 20(1):100–104

    Article  PubMed  CAS  Google Scholar 

  18. Lütjen-Drecoll E (1998) Functional morphology of the trabecular meshwork in primate eyes. Prog Ret Eye Res 18(1):91–119

    Article  Google Scholar 

  19. Maatta M, Tervahartiala T, Harju M, Airaksinen J, Autio-Harmainen H, Sorsa T (2005) Matrix metalloproteinases and their tissue inhibitors in aqueous humor of patients with primary open-angle glaucoma, exfoliation syndrome and exfoliation glaucoma. J Glaucoma 14(1):64–69

    Article  PubMed  Google Scholar 

  20. McCawley LJ, Matrisian LM (2001) Matrix metalloproteinases: they’re not just for matrix anymore! Curr Opin Cell Biol 13(5):534–540

    Article  PubMed  CAS  Google Scholar 

  21. Mohammed FF, Smookler DS, Khokha R (2003) Metalloproteinases, inflammation, and rheumatoid arthritis. Ann Rheum Dis 62(Suppl II):ii43–ii47

    PubMed  CAS  Google Scholar 

  22. Murphy G, Ward R, Hembry RM, Reynolds JJ, Kuhn K, Tryggvason K (1989) Characterization of gelatinase from pig polymorphonuclear leucocytes. A metalloproteinase resembling tumour type IV collagenase. Biochem J 258(2):463–472

    PubMed  CAS  Google Scholar 

  23. Nagase H, Woessner JF Jr (1999) Matrix metalloproteinases. J Biol Chem 274(31):21491–21494

    Article  PubMed  CAS  Google Scholar 

  24. Okada Y, Nagase H, Harris ED Jr (1986) A metalloproteinase from human rheumatoid synovial fibroblasts that digests connective tissue matrix components. Purification and characterization. J Biol Chem 261(30):14245–14255

    PubMed  CAS  Google Scholar 

  25. Pang IH, Hellberg PE, Fleenor DL, Jacobson N, Clark AF (2003) Expression of matrix metalloproteinases and their inhibitors in human trabecular meshwork cells. Invest Ophthalmol Vis Sci 44(8):3485–3493

    Article  PubMed  Google Scholar 

  26. Ritch R, Schlötzer-Schrehardt U (2001) Exfoliation syndrome. Surv Ophthalmol 45(4):265–315

    Article  PubMed  CAS  Google Scholar 

  27. Ritch R, Schlötzer-Schrehardt U, Konstas AGP (2003) Why is glaucoma associated with exfoliation syndrome? Prog Retin Eye Res 22(3):253–275

    Article  PubMed  Google Scholar 

  28. Samples JR, Alexander JP, Acott TS (1993) Regulation of the levels of human trabecular matrix metalloproteinases and inhibitor by interleukin-1 and dexamethasone. Invest Ophthalmol Vis Sci 34(12):3386–3395

    PubMed  CAS  Google Scholar 

  29. Schlötzer-Schrehardt U, Lommantzsch J, Kühle M, Konstans AGP, Naumann GOH (2003) Matrix metalloproteinases and their inhibitors in aqueous humor of patients with pseudoexfoliation syndrome/glaucoma and primary open-angle glaucoma. Invest Ophthalmol Vis Sci 44(3):1117–1125

    Article  PubMed  Google Scholar 

  30. Seiki M (2003) Membrane-type 1 matrix metalloproteinase: a key enzyme for tumor invasion. Cancer Lett 194(1):1–11

    Article  PubMed  CAS  Google Scholar 

  31. Sivak JM, Fini ME (2002) MMPs in the eye: emerging roles for matrix metalloproteinases in ocular physiology. Prog Retin Eye Res 21(1):1–14

    Article  PubMed  CAS  Google Scholar 

  32. Szekanecz Z, Halloran MM, Haskell CJ, Shah MR, Polverini PJ, Koch AE (1999) Mediators of angiogenesis: the role of cellular adhesion molecules. Trends Glycosci Glycotechnol 11(58):73–93

    CAS  Google Scholar 

  33. Tarkkanen A (1962) Pseudoexfoliation of the lens capsule. A clinical study of 418 patients with special reference to glaucoma, cataract, and changes of the vitreous. Acta Ophthalmol (Copenh) Suppl 71:1–98

    CAS  Google Scholar 

  34. Tsuruda TT, Costello-Boerrigter LC, Burnett JC Jr (2004) Matrix metalloproteinases: pathways of induction by bioactive molecules. Heart Fail Rev 9(1):53–61

    Article  PubMed  CAS  Google Scholar 

  35. Visse R, Nagase H (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 92(8):827–839

    Article  PubMed  CAS  Google Scholar 

  36. Vu TH, Werb Z (2000) Matrix metalloproteinases: effectors of development and normal physiology. Genes Dev 14(17):2123–2133

    Article  PubMed  CAS  Google Scholar 

  37. Weinreb RN, Khaw PT (2004) Primary open-angle glaucoma. Lancet 363(9422):1711–1720

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Agency of Technology, the Finnish Eye Research Foundation, EVO Funds from Kuopio University Hospital, and the Else-My Björn Eye Research Fund. The authors are grateful to Anne-Mari Haapaniemi, Anne Kaakkola, Tiina Sistonen, Helvi Käsnänen, and Aija Parkkinen for technical assistance, and to Ewen MacDonald, D. Pharm., for revising the English language of the manuscript.

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Correspondence to Seppo Rönkkö.

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Rönkkö, S., Rekonen, P., Kaarniranta, K. et al. Matrix metalloproteinases and their inhibitors in the chamber angle of normal eyes and patients with primary open-angle glaucoma and exfoliation glaucoma. Graefe's Arch Clin Exp Ophthalmol 245, 697–704 (2007). https://doi.org/10.1007/s00417-006-0440-1

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  • DOI: https://doi.org/10.1007/s00417-006-0440-1

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