Skip to main content
NCBI home page
The British Journal of Ophthalmology logoLink to The British Journal of Ophthalmology
. 2001 Feb;85(2):147–153. doi: 10.1136/bjo.85.2.147

Tear film MMP accumulation and corneal disease

V Smith 1, H Rishmawi 1, H Hussein 1, D Easty 1
PMCID: PMC1723854  PMID: 11159476

Abstract

BACKGROUND/AIMS—Matrix metalloproteinases (MMPs) accumulate in the tears of patients with active peripheral ulcerative keratitis (PUK) but it is unknown whether these enzymes have a central role in disease progression. The aims of the present investigation were to determine the source of these enzymes and to ascertain whether their accumulation in tears is a phenomenon specific to PUK or a general feature of other anterior segment diseases.
METHODS—The experimental samples were obtained from the culture media of conjunctival and corneal epithelial cells, from fractionated blood plasma and leucocytes of healthy subjects and patients with rheumatoid arthritis, and from the tears of healthy subjects and patients with a variety of anterior segment diseases. The MMPs of all samples were visualised by zymography and tear samples were assayed using nitrophenol acetate and an MMP-9 susceptible quenched fluorescent peptide as substrate.
RESULTS—The major MMPs that accumulate in the tears of patients with rheumatoid arthritis with active ocular disease are MMP-9 and a species of Mr 116 000. By comparing the zymographic activity profiles of the gelatinases present in the samples obtained, it was deduced that the main source of these MMPs was granulocytes. Their accumulation in tears was not unique to patients with PUK; detectable amounts of the enzymes also occurred in the tears of patients with keratoconus with associated atopic disease, patients undergoing treatment for herpetic eye disease, and patients with systemic and non-systemic dry eye disease.
CONCLUSION—The MMPs that accumulate in tears are mainly derived from granulocytes. This may be effected by autoimmune diseases that involve ocular tissue or by ocular diseases that induce an inflammatory response.



Full Text

The Full Text of this article is available as a PDF (157.1 KB).

Figure 1  .

Figure 1  

Open in a new tab

Representative zymographic gelatinase activity profiles of the MMPs secreted by primary cultures of conjunctival cells (gel A, lanes 1 and 2) and corneal epithelial cells (gel B, lane 1: cultured in MEM medium; lane 2: cultured in high Ca2+ MEM medium which partially induces enzyme activation).

Figure 2  .

Figure 2  

Open in a new tab

Representative zymographic gelatinase activity profiles of the MMPs produced by (A) granulocytes, (B) monocytes, (C) blood plasma, and (D) tears of patients with rheumatoid arthritis.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berman M. B. Regulation of corneal fibroblast MMP-1 secretion by cytochalasins. Cornea. 1994 Jan;13(1):51–57. doi: 10.1097/00003226-199401000-00009. [DOI] [PubMed] [Google Scholar]
  2. Berman M., Leary R., Gage J. Collagenase from corneal cell cultures and its modulation by phagocytosis. Invest Ophthalmol Vis Sci. 1979 Jun;18(6):588–601. [PubMed] [Google Scholar]
  3. Collier I. E., Wilhelm S. M., Eisen A. Z., Marmer B. L., Grant G. A., Seltzer J. L., Kronberger A., He C. S., Bauer E. A., Goldberg G. I. H-ras oncogene-transformed human bronchial epithelial cells (TBE-1) secrete a single metalloprotease capable of degrading basement membrane collagen. J Biol Chem. 1988 May 15;263(14):6579–6587. [PubMed] [Google Scholar]
  4. Dean D. D., Martel-Pelletier J., Pelletier J. P., Howell D. S., Woessner J. F., Jr Evidence for metalloproteinase and metalloproteinase inhibitor imbalance in human osteoarthritic cartilage. J Clin Invest. 1989 Aug;84(2):678–685. doi: 10.1172/JCI114215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gall B. G., Hartl D. L. Regulation of newly evolved enzymes. II. The ebg repressor. Genetics. 1975 Nov;81(3):427–435. doi: 10.1093/genetics/81.3.427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. John S. L., Morgan K., Tullo A. B., Holt P. J. Corneal autoimmunity in patients with peripheral ulcerative keratitis (PUK) in association with rheumatoid arthritis and Wegener's granulomatosis. Eye (Lond) 1992;6(Pt 6):630–636. doi: 10.1038/eye.1992.136. [DOI] [PubMed] [Google Scholar]
  7. Knight C. G., Willenbrock F., Murphy G. A novel coumarin-labelled peptide for sensitive continuous assays of the matrix metalloproteinases. FEBS Lett. 1992 Jan 27;296(3):263–266. doi: 10.1016/0014-5793(92)80300-6. [DOI] [PubMed] [Google Scholar]
  8. Liotta L. A., Steeg P. S., Stetler-Stevenson W. G. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell. 1991 Jan 25;64(2):327–336. doi: 10.1016/0092-8674(91)90642-c. [DOI] [PubMed] [Google Scholar]
  9. Maeda H., Okamoto T., Akaike T. Human matrix metalloprotease activation by insults of bacterial infection involving proteases and free radicals. Biol Chem. 1998 Feb;379(2):193–200. doi: 10.1515/bchm.1998.379.2.193. [DOI] [PubMed] [Google Scholar]
  10. Matrisian L. M., Bowden G. T., Krieg P., Fürstenberger G., Briand J. P., Leroy P., Breathnach R. The mRNA coding for the secreted protease transin is expressed more abundantly in malignant than in benign tumors. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9413–9417. doi: 10.1073/pnas.83.24.9413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Matrisian L. M. Metalloproteinases and their inhibitors in matrix remodeling. Trends Genet. 1990 Apr;6(4):121–125. doi: 10.1016/0168-9525(90)90126-q. [DOI] [PubMed] [Google Scholar]
  12. Matrisian L. M. The matrix-degrading metalloproteinases. Bioessays. 1992 Jul;14(7):455–463. doi: 10.1002/bies.950140705. [DOI] [PubMed] [Google Scholar]
  13. Matsumoto K., Shams N. B., Hanninen L. A., Kenyon K. R. Proteolytic activation of corneal matrix metalloproteinase by Pseudomonas aeruginosa elastase. Curr Eye Res. 1992 Nov;11(11):1105–1109. doi: 10.3109/02713689209015082. [DOI] [PubMed] [Google Scholar]
  14. Murphy G. J., Murphy G., Reynolds J. J. The origin of matrix metalloproteinases and their familial relationships. FEBS Lett. 1991 Sep 2;289(1):4–7. doi: 10.1016/0014-5793(91)80895-a. [DOI] [PubMed] [Google Scholar]
  15. Murphy G., Ward R., Hembry R. M., Reynolds J. J., Kühn K., Tryggvason K. Characterization of gelatinase from pig polymorphonuclear leucocytes. A metalloproteinase resembling tumour type IV collagenase. Biochem J. 1989 Mar 1;258(2):463–472. doi: 10.1042/bj2580463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Reynolds I., John S. L., Tullo A. B., Ayad S., Morgan K., Ballardie F. W., Holt P. J., Hillarby M. C. Characterization of two corneal epithelium-derived antigens associated with vasculitis. Invest Ophthalmol Vis Sci. 1998 Dec;39(13):2594–2601. [PubMed] [Google Scholar]
  17. Riley G. P., Harrall R. L., Watson P. G., Cawston T. E., Hazleman B. L. Collagenase (MMP-1) and TIMP-1 in destructive corneal disease associated with rheumatoid arthritis. Eye (Lond) 1995;9(Pt 6):703–718. doi: 10.1038/eye.1995.182. [DOI] [PubMed] [Google Scholar]
  18. Sakamoto S., Sakamoto M. Degradative processes of connective tissue proteins with special emphasis on collagenolysis and bone resorption. Mol Aspects Med. 1988;10(4):299–428. doi: 10.1016/0098-2997(88)90025-8. [DOI] [PubMed] [Google Scholar]
  19. Smith V. A., Hoh H. B., Easty D. L. Role of ocular matrix metalloproteinases in peripheral ulcerative keratitis. Br J Ophthalmol. 1999 Dec;83(12):1376–1383. doi: 10.1136/bjo.83.12.1376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Smith V. A., Hoh H. B., Littleton M., Easty D. L. Over-expression of a gelatinase A activity in keratoconus. Eye (Lond) 1995;9(Pt 4):429–433. doi: 10.1038/eye.1995.100. [DOI] [PubMed] [Google Scholar]
  21. Unemori E. N., Werb Z. Reorganization of polymerized actin: a possible trigger for induction of procollagenase in fibroblasts cultured in and on collagen gels. J Cell Biol. 1986 Sep;103(3):1021–1031. doi: 10.1083/jcb.103.3.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Woessner J. F., Jr Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J. 1991 May;5(8):2145–2154. [PubMed] [Google Scholar]

Articles from The British Journal of Ophthalmology are provided here courtesy of BMJ Publishing Group

RESOURCES