Skip to main content
The British Journal of Ophthalmology logoLink to The British Journal of Ophthalmology
. 1993 Apr;77(4):238–242. doi: 10.1136/bjo.77.4.238

Origin of fibronectin in epiretinal membranes of proliferative vitreoretinopathy and proliferative diabetic retinopathy.

S Grisanti 1, K Heimann 1, P Wiedemann 1
PMCID: PMC504489  PMID: 8494861

Abstract

Fibronectins, high molecular multifunctional glycoproteins of the extracellular matrix and plasma, have been a popular area of research in the pathogenesis of proliferative disorders of the retina. Several immunohistochemical studies have revealed that fibronectin is a major constituent of epiretinal membranes and that the cell types involved in proliferative intraocular disorders may synthesise it. However, owing to the fact that plasma and cellular fibronectin are similar in their overall structure, the origin of fibronectin in epiretinal membranes has not yet been clearly defined. In this study, we used two monoclonal antibodies: FN-3, which recognises an extra domain present in the cellular but not plasma form of fibronectin; and FN-4, which reacts with an antigenic site on both plasma and cellular fibronectin. In 37 epiretinal membranes obtained from eyes with proliferative vitreoretinopathy and proliferative diabetic retinopathy, we demonstrated the presence of cellular fibronectin, thus indicating local production. The significantly stronger and positive immunostain with FN-4 in the same specimens suggests the colocalisation of plasma fibronectin, that may be derived from the breakdown of the blood-retinal barrier and trapped in membranes during their formation. In pathological vitreous we demonstrated both types of fibronectin by western blot analysis.

Full text

PDF
238

Images in this article

Selected References

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

  1. Akiyama S. K., Yamada K. M. Fibronectin. Adv Enzymol Relat Areas Mol Biol. 1987;59:1–57. doi: 10.1002/9780470123058.ch1. [DOI] [PubMed] [Google Scholar]
  2. Alitalo K., Hovi T., Vaheri A. Fibronectin is produced by human macrophages. J Exp Med. 1980 Mar 1;151(3):602–613. doi: 10.1084/jem.151.3.602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Atherton B. T., Hynes R. O. A difference between plasma and cellular fibronectins located with monoclonal antibodies. Cell. 1981 Jul;25(1):133–141. doi: 10.1016/0092-8674(81)90237-3. [DOI] [PubMed] [Google Scholar]
  4. Campochiaro P. A., Jerdan J. A., Glaser B. M., Cardin A., Michels R. G. Vitreous aspirates from patients with proliferative vitreoretinopathy stimulate retinal pigment epithelial cell migration. Arch Ophthalmol. 1985 Sep;103(9):1403–1405. doi: 10.1001/archopht.1985.01050090155053. [DOI] [PubMed] [Google Scholar]
  5. Campochiaro P. A., Jerdan J. A., Glaser B. M. Serum contains chemoattractants for human retinal pigment epithelial cells. Arch Ophthalmol. 1984 Dec;102(12):1830–1833. doi: 10.1001/archopht.1984.01040031488029. [DOI] [PubMed] [Google Scholar]
  6. Campochiaro P. A., Jerdon J. A., Glaser B. M. The extracellular matrix of human retinal pigment epithelial cells in vivo and its synthesis in vitro. Invest Ophthalmol Vis Sci. 1986 Nov;27(11):1615–1621. [PubMed] [Google Scholar]
  7. Cordell J. L., Falini B., Erber W. N., Ghosh A. K., Abdulaziz Z., MacDonald S., Pulford K. A., Stein H., Mason D. Y. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984 Feb;32(2):219–229. doi: 10.1177/32.2.6198355. [DOI] [PubMed] [Google Scholar]
  8. D'Ardenne A. J., McGee J. O. Fibronectin in disease. J Pathol. 1984 Apr;142(4):235–251. doi: 10.1002/path.1711420402. [DOI] [PubMed] [Google Scholar]
  9. Engvall E., Ruoslahti E., Miller E. J. Affinity of fibronectin to collagens of different genetic types and to fibrinogen. J Exp Med. 1978 Jun 1;147(6):1584–1595. doi: 10.1084/jem.147.6.1584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Görg A., Postel W., Westermeier R., Gianazza E., Righetti P. G. Gel gradient electrophoresis, isoelectric focusing and two-dimensional techniques in horizontal, ultrathin polyacrylamide layers. J Biochem Biophys Methods. 1980 Nov;3(5):273–284. doi: 10.1016/0165-022x(80)90008-1. [DOI] [PubMed] [Google Scholar]
  11. Hayashi M., Yamada K. M. Differences in domain structures between plasma and cellular fibronectins. J Biol Chem. 1981 Nov 10;256(21):11292–11300. [PubMed] [Google Scholar]
  12. Hiscott P. S., Grierson I., McLeod D. Natural history of fibrocellular epiretinal membranes: a quantitative, autoradiographic, and immunohistochemical study. Br J Ophthalmol. 1985 Nov;69(11):810–823. doi: 10.1136/bjo.69.11.810. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hiscott P., Waller H. A., Grierson I., Butler M. G., Scott D. Local production of fibronectin by ectopic human retinal cells. Cell Tissue Res. 1992 Jan;267(1):185–192. doi: 10.1007/BF00318703. [DOI] [PubMed] [Google Scholar]
  14. Hynes R. O., Destree A. Extensive disulfide bonding at the mammalian cell surface. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2855–2859. doi: 10.1073/pnas.74.7.2855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Immonen I., Tervo K., Virtanen I., Laatikainen L., Tervo T. Immunohistochemical demonstration of cellular fibronectin and tenascin in human epiretinal membranes. Acta Ophthalmol (Copenh) 1991 Aug;69(4):466–471. doi: 10.1111/j.1755-3768.1991.tb02024.x. [DOI] [PubMed] [Google Scholar]
  16. Keen J., Chang S. E., Taylor-Papadimitriou J. Monoclonal antibodies that distinguish between human cellular and plasma fibronectin. Mol Biol Med. 1984 Feb;2(1):15–27. [PubMed] [Google Scholar]
  17. Kornblihtt A. R., Vibe-Pedersen K., Baralle F. E. Human fibronectin: molecular cloning evidence for two mRNA species differing by an internal segment coding for a structural domain. EMBO J. 1984 Jan;3(1):221–226. doi: 10.1002/j.1460-2075.1984.tb01787.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kornblihtt A. R., Vibe-Pedersen K., Baralle F. E. Isolation and characterization of cDNA clones for human and bovine fibronectins. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3218–3222. doi: 10.1073/pnas.80.11.3218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Oh E., Pierschbacher M., Ruoslahti E. Deposition of plasma fibronectin in tissues. Proc Natl Acad Sci U S A. 1981 May;78(5):3218–3221. doi: 10.1073/pnas.78.5.3218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Scheiffarth O. F., Kampik A., Günther H., von der Mark K. Proteins of the extracellular matrix in vitreoretinal membranes. Graefes Arch Clin Exp Ophthalmol. 1988;226(4):357–361. doi: 10.1007/BF02172967. [DOI] [PubMed] [Google Scholar]
  21. Schwarzbauer J. E., Tamkun J. W., Lemischka I. R., Hynes R. O. Three different fibronectin mRNAs arise by alternative splicing within the coding region. Cell. 1983 Dec;35(2 Pt 1):421–431. doi: 10.1016/0092-8674(83)90175-7. [DOI] [PubMed] [Google Scholar]
  22. Stenman S., Vaheri A. Fibronectin in human solid tumors. Int J Cancer. 1981;27(4):427–435. doi: 10.1002/ijc.2910270403. [DOI] [PubMed] [Google Scholar]
  23. Tamkun J. W., Hynes R. O. Plasma fibronectin is synthesized and secreted by hepatocytes. J Biol Chem. 1983 Apr 10;258(7):4641–4647. [PubMed] [Google Scholar]
  24. Towbin H., Gordon J. Immunoblotting and dot immunobinding--current status and outlook. J Immunol Methods. 1984 Sep 4;72(2):313–340. doi: 10.1016/0022-1759(84)90001-2. [DOI] [PubMed] [Google Scholar]
  25. Vartio T., Laitinen L., Närvänen O., Cutolo M., Thornell L. E., Zardi L., Virtanen I. Differential expression of the ED sequence-containing form of cellular fibronectin in embryonic and adult human tissues. J Cell Sci. 1987 Nov;88(Pt 4):419–430. doi: 10.1242/jcs.88.4.419. [DOI] [PubMed] [Google Scholar]
  26. Weller M., Heimann K., Wiedemann P. Immunochemical studies of epiretinal membranes using APAAP complexes: evidence for macrophage involvement in traumatic proliferative vitreoretinopathy. Int Ophthalmol. 1988 Jan;11(3):181–186. doi: 10.1007/BF00130621. [DOI] [PubMed] [Google Scholar]
  27. Weller M., Wiedemann P., Heimann K. Proliferative vitreoretinopathy--is it anything more than wound healing at the wrong place? Int Ophthalmol. 1990 Mar;14(2):105–117. doi: 10.1007/BF00154210. [DOI] [PubMed] [Google Scholar]
  28. Weller M., Wiedemann P., Heimann K., Zilles K. The significance of fibronectin in vitreoretinal pathology. A critical evaluation. Graefes Arch Clin Exp Ophthalmol. 1988;226(3):294–298. doi: 10.1007/BF02181200. [DOI] [PubMed] [Google Scholar]
  29. Yamada K. M., Akiyama S. K., Hasegawa T., Hasegawa E., Humphries M. J., Kennedy D. W., Nagata K., Urushihara H., Olden K., Chen W. T. Recent advances in research on fibronectin and other cell attachment proteins. J Cell Biochem. 1985;28(2):79–97. doi: 10.1002/jcb.240280202. [DOI] [PubMed] [Google Scholar]
  30. Yamada K. M., Kennedy D. W. Fibroblast cellular and plasma fibronectins are similar but not identical. J Cell Biol. 1979 Feb;80(2):492–498. doi: 10.1083/jcb.80.2.492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Yamada K. M., Olden K. Fibronectins--adhesive glycoproteins of cell surface and blood. Nature. 1978 Sep 21;275(5677):179–184. doi: 10.1038/275179a0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES