Tissue inhibitor of metalloproteinases-3 is a component of Bruch's membrane of the eye (original) (raw)

. 1997 Jan;150(1):323–328.

Abstract

Mutations in tissue inhibitor of metalloproteinases (TIMP)-3 are found in some patients with Sorsby's fundus dystrophy, a retinal degeneration characterized by abnormal deposits in Bruch's membrane and choroidal neovascularization. The purpose of this study was to localize TIMP-3 in the retina/choroid of normal human and animal eyes. Immunolabeling was performed on unfixed and fixed sections of human eyes aged 24 to 85 years and unfixed sections of baboon, chicken, cow, pig, and rat eyes using a monoclonal antibody against a human TIMP-3 synthetic peptide. The antibody produced strong immunolabeling of Bruch's membrane and drusen and weak labeling of retina blood vessels in unfixed human and baboon eyes. Unfixed chicken, cow, pig, and rat tissues showed no reactivity. After antigen retrieval, all fixed human eyes showed specific labeling of Bruch's membrane and drusen, which was strongest in eyes from elderly donors. The results indicate that TIMP-3 is an extracellular matrix component of Bruch's membrane. Thus, abnormal local function of TIMP-3 may lead to the characteristic Bruch's membrane deposits and choroidal neovascularization found in Sorsby's fundus dystrophy. Specific labeling of drusen raises the possibility that altered TIMP-3-mediated matrix remodeling may contribute to age-related degenerative changes in Bruch's membrane.

323

Images in this article

Selected References

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

  1. Acott T. S., Weleber R. G. Vitamin A megatherapy for retinal abnormalities. Nat Med. 1995 Sep;1(9):884–885. doi: 10.1038/nm0995-884. [DOI] [PubMed] [Google Scholar]
  2. Apte S. S., Hayashi K., Seldin M. F., Mattei M. G., Hayashi M., Olsen B. R. Gene encoding a novel murine tissue inhibitor of metalloproteinases (TIMP), TIMP-3, is expressed in developing mouse epithelia, cartilage, and muscle, and is located on mouse chromosome 10. Dev Dyn. 1994 Jul;200(3):177–197. doi: 10.1002/aja.1002000302. [DOI] [PubMed] [Google Scholar]
  3. Apte S. S., Mattei M. G., Olsen B. R. Cloning of the cDNA encoding human tissue inhibitor of metalloproteinases-3 (TIMP-3) and mapping of the TIMP3 gene to chromosome 22. Genomics. 1994 Jan 1;19(1):86–90. doi: 10.1006/geno.1994.1016. [DOI] [PubMed] [Google Scholar]
  4. Apte S. S., Olsen B. R., Murphy G. The gene structure of tissue inhibitor of metalloproteinases (TIMP)-3 and its inhibitory activities define the distinct TIMP gene family. J Biol Chem. 1995 Jun 16;270(24):14313–14318. doi: 10.1074/jbc.270.24.14313. [DOI] [PubMed] [Google Scholar]
  5. Bressler N. M., Silva J. C., Bressler S. B., Fine S. L., Green W. R. Clinicopathologic correlation of drusen and retinal pigment epithelial abnormalities in age-related macular degeneration. Retina. 1994;14(2):130–142. [PubMed] [Google Scholar]
  6. Capon M. R., Marshall J., Krafft J. I., Alexander R. A., Hiscott P. S., Bird A. C. Sorsby's fundus dystrophy. A light and electron microscopic study. Ophthalmology. 1989 Dec;96(12):1769–1777. doi: 10.1016/s0161-6420(89)32664-9. [DOI] [PubMed] [Google Scholar]
  7. Carrero-Valenzuela R. D., Klein M. L., Weleber R. G., Murphey W. H., Litt M. Sorsby fundus dystrophy. A family with the Ser181Cys mutation of the tissue inhibitor of metalloproteinases 3. Arch Ophthalmol. 1996 Jun;114(6):737–738. doi: 10.1001/archopht.1996.01100130729016. [DOI] [PubMed] [Google Scholar]
  8. Della N. G., Campochiaro P. A., Zack D. J. Localization of TIMP-3 mRNA expression to the retinal pigment epithelium. Invest Ophthalmol Vis Sci. 1996 Aug;37(9):1921–1924. [PubMed] [Google Scholar]
  9. Green W. R., Enger C. Age-related macular degeneration histopathologic studies. The 1992 Lorenz E. Zimmerman Lecture. Ophthalmology. 1993 Oct;100(10):1519–1535. doi: 10.1016/s0161-6420(93)31466-1. [DOI] [PubMed] [Google Scholar]
  10. Hayakawa T., Yamashita K., Ohuchi E., Shinagawa A. Cell growth-promoting activity of tissue inhibitor of metalloproteinases-2 (TIMP-2). J Cell Sci. 1994 Sep;107(Pt 9):2373–2379. doi: 10.1242/jcs.107.9.2373. [DOI] [PubMed] [Google Scholar]
  11. Jacobson S. G., Cideciyan A. V., Regunath G., Rodriguez F. J., Vandenburgh K., Sheffield V. C., Stone E. M. Night blindness in Sorsby's fundus dystrophy reversed by vitamin A. Nat Genet. 1995 Sep;11(1):27–32. doi: 10.1038/ng0995-27. [DOI] [PubMed] [Google Scholar]
  12. Kishnani N. S., Staskus P. W., Yang T. T., Masiarz F. R., Hawkes S. P. Identification and characterization of human tissue inhibitor of metalloproteinase-3 and detection of three additional metalloproteinase inhibitor activities in extracellular matrix. Matrix Biol. 1995 Feb;14(6):479–488. doi: 10.1016/0945-053x(95)90005-5. [DOI] [PubMed] [Google Scholar]
  13. Kliffen M., Mooy C. M., Luider T. M., Huijmans J. G., Kerkvliet S., de Jong P. T. Identification of glycosaminoglycans in age-related macular deposits. Arch Ophthalmol. 1996 Aug;114(8):1009–1014. doi: 10.1001/archopht.1996.01100140217021. [DOI] [PubMed] [Google Scholar]
  14. Leco K. J., Khokha R., Pavloff N., Hawkes S. P., Edwards D. R. Tissue inhibitor of metalloproteinases-3 (TIMP-3) is an extracellular matrix-associated protein with a distinctive pattern of expression in mouse cells and tissues. J Biol Chem. 1994 Mar 25;269(12):9352–9360. [PubMed] [Google Scholar]
  15. Newsome D. A., Hewitt A. T., Huh W., Robey P. G., Hassell J. R. Detection of specific extracellular matrix molecules in drusen, Bruch's membrane, and ciliary body. Am J Ophthalmol. 1987 Oct 15;104(4):373–381. doi: 10.1016/0002-9394(87)90227-3. [DOI] [PubMed] [Google Scholar]
  16. Pavloff N., Staskus P. W., Kishnani N. S., Hawkes S. P. A new inhibitor of metalloproteinases from chicken: ChIMP-3. A third member of the TIMP family. J Biol Chem. 1992 Aug 25;267(24):17321–17326. [PubMed] [Google Scholar]
  17. Peters A. L., Greenberg J. Sorsby's fundus dystrophy. A South African family with a point mutation on the tissue inhibitor of metalloproteinases-3 gene on chromosome 22. Retina. 1995;15(6):480–485. [PubMed] [Google Scholar]
  18. Polkinghorne P. J., Capon M. R., Berninger T., Lyness A. L., Sehmi K., Bird A. C. Sorsby's fundus dystrophy. A clinical study. Ophthalmology. 1989 Dec;96(12):1763–1768. doi: 10.1016/s0161-6420(89)32654-6. [DOI] [PubMed] [Google Scholar]
  19. Ruiz A., Brett P., Bok D. TIMP-3 is expressed in the human retinal pigment epithelium. Biochem Biophys Res Commun. 1996 Sep 13;226(2):467–474. doi: 10.1006/bbrc.1996.1379. [DOI] [PubMed] [Google Scholar]
  20. Shi S. R., Imam S. A., Young L., Cote R. J., Taylor C. R. Antigen retrieval immunohistochemistry under the influence of pH using monoclonal antibodies. J Histochem Cytochem. 1995 Feb;43(2):193–201. doi: 10.1177/43.2.7822775. [DOI] [PubMed] [Google Scholar]
  21. Shi S. R., Key M. E., Kalra K. L. Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem. 1991 Jun;39(6):741–748. doi: 10.1177/39.6.1709656. [DOI] [PubMed] [Google Scholar]
  22. Steinmetz R. L., Polkinghorne P. C., Fitzke F. W., Kemp C. M., Bird A. C. Abnormal dark adaptation and rhodopsin kinetics in Sorsby's fundus dystrophy. Invest Ophthalmol Vis Sci. 1992 Apr;33(5):1633–1636. [PubMed] [Google Scholar]
  23. Weber B. H., Vogt G., Pruett R. C., Stöhr H., Felbor U. Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP3) in patients with Sorsby's fundus dystrophy. Nat Genet. 1994 Dec;8(4):352–356. doi: 10.1038/ng1294-352. [DOI] [PubMed] [Google Scholar]