Parasitology Research

, Volume 118, Issue 2, pp 483–491 | Cite as

Matrix metalloproteinase-2 and matrix metalloproteinase-9 in mice with ocular toxocariasis

  • Ling-Yuh Shyu
  • Ke-Min Chen
  • Shih-Chan LaiEmail author
Helminthology - Original Paper


In ocular toxocariasis, Toxocara canis-induced inflammatory reaction can lead to eye destruction and granuloma, which is formed by immune cell infiltration and concurrent extensive remodeling tissue. Herein, the histomorphology of granuloma and proteinase production in the eye of T. canis-infected BALB/c mice were investigated. Pathological effects substantially increased after the infection culminated in a severe leukocyte infiltration and granuloma formation from days 4 to 56 post-inoculation. The matrix metalloproteinase (MMP)-2 and MMP-9 activities remarkably increased, compared with those of uninfected control, by gelatin zymography and Western blot analysis in ocular toxocariasis. Granuloma formation had a remarkably positive correlation with MMP-2 and MMP-9 levels. We suggested that T. canis larvae and leukocytes infiltrated from blood vessel both migrated into corpus adiposum orbitae. Activated leukocytes secreted MMP-2 and MMP-9, leading to fibronectin degradation. The imbalance of MMP-2/TIMP-2 and MMP-9/TIMP-1 may play a role in inflammatory cell infiltration and extracellular matrix degradation, forming granuloma, in ophthalmological pathogenesis of T. canis infection.


Fibronectin Granuloma Metalloproteinase Ocular Toxocara canis 



We wish to thank Ping-Sung Chiu of the Department of Parasitology, Chung Shan Medical University for providing an invaluable assistance in the conduct of this study. This work was supported by the Intramural Research Program of Chung Shan Medical University, Taichung, Taiwan (CSMU-INT-106-04).

Compliance with ethical standards

The manuscript does not contain clinical studies or patient data.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Ashton N (1960) Larval granulomatosis of the retina due to Toxocara. Br J Ophthalmol 44:129–148CrossRefGoogle Scholar
  2. Barletta JP, Angella G, Balch K, Dimora HG, Stern GA, Moser MT (1996) Inhibition of pseudomonal ulceration in rabbit corneas by a synthetic matrix metalloproteinase inhibitor. Invest Ophthalmol Vis Sci 37:20–28Google Scholar
  3. Brew K, Dinakarpandian D, Nagase H (2000) Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta Prot Struct Mol Enzymol 1477:267–283CrossRefGoogle Scholar
  4. Cauwe B, Van Den Steen PE, Opdenakker G (2007) The biochemical, biological and pathological kaleidoscope of cell surface substrates processed by matrix metalloproteinases. Crit Rev Biochem Mol Biol 42:113–185CrossRefGoogle Scholar
  5. Chiu PS, Lai SC (2013) Matrix metalloproteinase-9 leads to claudin-5 degradation via the NF-κB pathway in BALB/c mice with eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis. PLoS One 8:e53370CrossRefGoogle Scholar
  6. Crouch E (1990) Pathobiology of pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 259:L159–L184CrossRefGoogle Scholar
  7. Despommier D (2003) Toxocariasis: clinical aspects, epidemiology, medical ecology, and molecular aspects. Clin Microbiol Rev 16:265–272CrossRefGoogle Scholar
  8. Di Girolamo N, Verma MJ, McCluskey PJ, Lloyd A, Wakefield D (1996) Increased matrix metalloproteinases in the aqueous humor of patients and experimental animals with uveitis. Curr Eye Res 15:1060–1068CrossRefGoogle Scholar
  9. Di Girolamo N, Lloyd A, McCluskey P, Filipic M, Wakefield D (1997) Increased expression of matrix metalloproteinases in vivo in scleritis tissue and in vitro in cultured human scleral fibroblasts. Am J Pathol 150:653–666Google Scholar
  10. Di Girolamo N, McCluskey P, Lloyd A, Coroneo MT, Wakefield D (2000) Expression of MMPs and TIMPs in human pterygia and cultured pterygium epithelial cells. Invest Ophthalmol Vis Sci 41:671–679Google Scholar
  11. Duguid TM (1961) Chronic endophthalmitis due to Toxocara. Br J Ophthalmol 45:705–717CrossRefGoogle Scholar
  12. Galvis V, Sherwin T, Tello A, Merayo J, Barrera R, Acera A (2015) Keratoconus: an inflammatory disorder? Eye (Lond) 29:843–859. CrossRefGoogle Scholar
  13. Gueders MM, Foidart JM, Noel A, Cataldo DD (2006) Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: potential implications in asthma and other lung diseases. Eur J Pharmacol 533(1–3):133–144CrossRefGoogle Scholar
  14. Hemmann S, Graf J, Roderfeld M, Roeb E (2007) Expression of MMPs and TIMPs in liver fibrosis—a systematic review with special emphasis on anti-fibrotic strategies. J Hepatol 46:955–975CrossRefGoogle Scholar
  15. Hsu LS, Lee HH, Chen KM, Chou HL, Lai SC (2005) Matrix metalloproteinase-2, and -9 in granulomatous fibrosis of rat infected with Angiostrongylus cantonensis. Ann Trop Med Parasitol 99:61–70CrossRefGoogle Scholar
  16. Izzo AA, Izzo LS, Kasimos J, Majka S (2004) A matrix metalloproteinase inhibitor promotes granuloma formation during the early phase of Mycobacterium tuberculosis pulmonary infection. Tuberculosis (Edinburgh) 84:387–396CrossRefGoogle Scholar
  17. Korpos E, Wu C, Sorokin L (2009) Multiple roles of the extracellular matrix in inflammation. Curr Pharm Des 15:1349–1357CrossRefGoogle Scholar
  18. Krauss AH, Woodward DF (1993) Polymorphonuclear leukocyte infiltration into the subretinal choroid and optic nerve in response to leukotrienes. Invest Ophthalmol Vis Sci 34:3679–3686Google Scholar
  19. Lalla RS, Garg RK, Malhotra HS, Jain A, Verma R, Pandey CM, Singh GP, Sharma PK (2015) Cytokines, MMP-2, and MMP-9 levels in patients with a solitary cysticercus granuloma. Neurol India 63:190–196CrossRefGoogle Scholar
  20. Ma JJ, Dohlman CH (2002) Mechanisms of corneal ulceration. Ophthalmol Clin N Am 15:27–33CrossRefGoogle Scholar
  21. Messmer EM, von Lindenfels V, Garbe A, Kampik A (2016) Matrix metalloproteinase 9 testing in dry eye disease using a commercially available point-of-care immunoassay. Ophthalmology 123:2300–2308. CrossRefGoogle Scholar
  22. Nasu-Tada K, Koizumi S, Tsuda M, Kunifusa E, Inoue K (2006) Possible involvement of increase in spinal fibronectin following peripheral nerve injury in upregulation of microglial P2X4, a key molecule for mechanical allodynia. Glia 53:769–775CrossRefGoogle Scholar
  23. Ollivier FJ, Gilger BC, Barrie KP, Kallberg ME, Plummer CE, O'Reilly S, Gelatt KN, Brooks DE (2007) Proteinases of the cornea and preocular tear film. Vet Ophthalmol 10:199–206CrossRefGoogle Scholar
  24. Parks WC, Wilson CL, López-Boado YS (2004) Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev Immunol 4:617–629CrossRefGoogle Scholar
  25. Pelletier JP, Mineau F, Faure MP, Martel-Pelletier J (1990) Imbalance between the mechanisms of activation and inhibition of metalloproteinases in the early lesions of experimental osteoarthritis. Arthritis Rheum 33:1466–1476CrossRefGoogle Scholar
  26. Ouaissi MA, Capron A (1985) Fibronectins: structure and function. Ann Inst Pasteur Immunol 136C:169–185CrossRefGoogle Scholar
  27. Rockey JH, Donnelly JJ, Stromberg BE, Soulsby EJ (1979) Immunopathology of Toxocara canis and Ascaris suum infections of the eye: the role of the eosinophil. Invest Ophthalmol Vis Sci 18:1172–1184Google Scholar
  28. Rockey JH, Donnelly JJ, Stromberg BE, Laties AM, Soulsby EJ (1981) Immunopathology of ascarid infection of the eye. Role of IgE antibodies and mast cells. Arch Ophthalmol 99:1831–1840CrossRefGoogle Scholar
  29. Savigny DH (1975) In vitro maintenance of Toxocara canis larvae and a simple method for the production of Toxocara ES antigen for use in serodiagnostic tests for visceral larva migrans. J Parasitol 61:781–782CrossRefGoogle Scholar
  30. Sivak JM, Fini ME (2002) MMPs in the eye: emerging roles for matrix metalloproteinases in ocular physiology. Prog Retin Eye Res 21:1–14CrossRefGoogle Scholar
  31. Wentworth JS, Paterson CA, Gray RD (1992) Effect of a metalloproteinase inhibitor on established corneal ulcers. Invest Ophthalmol Vis Sci 33:2174–2179Google Scholar
  32. Wong TT, Sethi C, Daniels JT, Limb GA, Murphy G, Khaw PT (2002) Matrix metalloproteinases in disease and repair processes in the anterior segment. Surv Ophthalmol 47:239–256CrossRefGoogle Scholar
  33. Yang YN, Bauer D, Wasmuth S, Steuhl KP, Heiligenhaus A (2003) Matrix metalloproteinases (MMP-2 and 9) and tissue inhibitors of matrix metalloproteinases (TIMP-1 and 2) during the course of experimental necrotizing herpetic keratitis. Exp Eye Res 77:227–237CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of ParasitologyChung Shan Medical UniversityTaichungTaiwan
  2. 2.Clinical LaboratoryChung Shan Medical University HospitalTaichungTaiwan

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