Skip to main content
SpringerLink
Log in

Proliferative response of cultured human tenon's capsule fibroblasts to platelet-derived growth factor isoforms

  • Laboratory Investigation
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

• Background: Although platelet-derived growth factor (PDGF) has been thought to be critical in the wound-healing response of Tenon's capsule fibroblasts after glaucoma filtration surgery, no information is currently available concerning the proliferative effect of PDGF isoforms on this cell type. The aim of the present study was to evaluate the proliferative effect of PDGF-AB heterodimer and PDGF-AA and -BB homodimers on cultured human Tenon's capsule fibroblasts. • Methods: Human Tenon's capsule fibroblasts, cultured under serum-free conditions, were stimulated with PDGF-AA, -AB and -BB isoforms in concentrations ranging from 1 to 100 ng/ml. Cell numbers were determined on days 1, 3, 5 and 7, using a cell counter. • Results: Addition of PDGF-AB and -BB led to a dosedependent increase in cell proliferation. A maximal response (79.9% over control) was obtained after 7 days with 30 ng/ml of PDGF-BB, with an EC50 of 8.9 ng/ml. The maximal increase in cell proliferation caused by PDGF-AB (30 ng/ml) was 54.9%, with an EC50 of 12.5 ng/ml. Stimulation with PDGF-AA revealed a significant effect only with concentrations higher than 30 ng/ml. • Conclusion: Our results indicate that PDGF-AB and -BB isoforms are potent stimulators of proliferation of human Tenon's capsule fibroblasts, suggesting that PDGF-AB and -BB isoforms play an important role in the wound-healing response after glaucoma filtration surgery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Addicks EM, Quigley HA, Green WR, Robin AL (1983) Histologic characteristics of filtering blebs in glaucomatous eyes. Arch Ophthalmol 101:795–798

    Google Scholar 

  2. Assouline M, Chew SJ, Thompson HW, Breuerman R (1992) Effect of growth factors on collagen lattice contration by human keratocytes. Invest Ophthalmol Vis Sci 33:1742–1755

    Google Scholar 

  3. Bauer EA, Cooper TW, Huang JS, Altman J, Deuel TF (1985) Stimulation of in vitro human skin collagenase expression by platelet-derived growth factor. Proc Natl Acad Sci USA 82:4132–4136

    Google Scholar 

  4. Cromack DT, Porras-Reyes B, Mustoe TA (1990) Current concepts in wound healing: growth factor and macrophage interaction. J Trauma 30:S129–133

    Google Scholar 

  5. Eriksson A, Nister M, Leveen P, Westermark B, Heldin CH, Claesson-Welch L (1991) Induction of platelet-derived growth factor α- and β-receptor mRNA and protein by platelet derived growth factor BB. J Biol Chem 266:21138–21144

    Google Scholar 

  6. Grotendorst GR, Igarashi A, Larson R, Soma Y, Charette M (1991) Differential binding, biological and biochemical actions of recombinant PDGF AA, AB, and BB molecules on connective tissue cells. J Cell Physiol 124:1841–1848

    Google Scholar 

  7. Hart CE, Forstrom JW, Kelly JD, Smith RA, Ross R, Murry MJ, Bowen-Pope DF (1988) Two classes of PDGF receptor recognize different isoforms of PDGF. Science 240:1529–1531

    Google Scholar 

  8. Heldin CH, Westermark B (1989) Platelet-derived growth factor: three isoforms and two receptor types. Trends Genet 5:108–111

    Google Scholar 

  9. Heldin CH, Westermark B (1991) Platelet-derived growth factor and autocrine mechanisms of oncogenic processes. Crit Rev Oncogenesis 2:109–124

    Google Scholar 

  10. Heldin CH, Wasteson A, Westermark B (1982) Interaction of platelet-derived growth factor with its fibroblast receptor: demonstration of ligand degradation and receptor modulation. J Biol Chem 257:4216–4221

    Google Scholar 

  11. Hoppe J, Weich HA, Eichner W (1989) Preparation of biologically active platelet-derived growth factor type BB from a fusion protein expressed inE. coli. Biochemistry 28:2956–2960

    Google Scholar 

  12. Hoppe J, Weich HA, Eichner W, Tatje D (1990) Preparation of biologically active platelet-derived growth factor isoforms AA and AB. Eur J Biochem 187:207–214

    Google Scholar 

  13. Hoppenreijs VPT, Pels E, Vrensen GJM, Felten PC, and Treffers WF (1993) Platelet-derived growth factor: receptor expression in cornea and effect on corneal cells. Invest Ophthalmol Vis Sci 34:637–649

    Google Scholar 

  14. Jampel HD, McGuigan LJB, Dunkelberger GR, L'Hernault N, Quigley HA (1988) Cellular proliferation after experimental glaucoma filtration surgery. Arch Ophthalmol 106:89–94

    Google Scholar 

  15. Khaw PT, Occleston NL, Schulz G, Gierson I, Sherwood MB, Larkin G (1994) Activation and suppression of fibroblast function. Eye 8:188–195

    Google Scholar 

  16. Knorr M, Wunderlich K, Steuhl, Thiel HJ, Hoppe J (1991) Lens epithelial cell response to PDGF isoforms in cell culture. ARVO Abstracts. Invest Ophthalmol Vis Sci 31:228

    Google Scholar 

  17. Knorr M, Hoppe J, Steuhl KP, Dartsch PC (1992) Effect of PDGF-AB heterodimer on a corneal epithelial cell line. Eur J Cell Biol 57:202–209

    Google Scholar 

  18. Knorr M, Steuhl KP, Tatje D, Hoppe J (1992) A rabbit corneal cell line expresses functional platelet-derived growth factor beta-type receptors. Invest Ophthalmol Vis Sci 33:2207–2211

    Google Scholar 

  19. Knorr M, Wunderlich K, Steuhl KP, Hoppe J (1993) Lens epithelial cell response to platelet-derived growth factor. Graefe's Arch Clin Exp Ophthalmol 231:424–428

    Google Scholar 

  20. Knorr M, Wunderlich K, Tatje D, Steuhl KP, Hoppe J, Thiel HJ (1994) Cultured lens epithelial cells express functional platelet-derived growth factor (PDGF) beta-type receptors. ARVO Abstracts. Invest Ophthalmol Vis Sci 33:1037

    Google Scholar 

  21. Martinet Y, Bitterman PB, Mornex JF, Grotendorst GR, Martin GR, Crystal RG (1986) Activated human monocytes express the cis-oncogene and release a mediator showing PDGF-like activity. Nature 319:158–160

    Google Scholar 

  22. McAvoy JW, Chamberlain CG (1990) Growth factors in the eye. Prog Growth Factor Res 2:29–43

    Google Scholar 

  23. Pierce GF, Mustoe TA, Altrock BW, Deuel TF, Thomason A (1991) Role of platelet-derived growth factor in wound healing. J Cell Biochem 45:319–326

    Google Scholar 

  24. Raines EW, Bowen-Pope DF, and Ross R (1990) Platelet-derived growth factors. In: Sporn MB, Roberts AB (eds) Peptide growth factors and their receptors. (Handbook of experimental pharmacology, vol 95) Springer, Berlin Heidelberg New York, pp 173–262

    Google Scholar 

  25. Ross R, Raines EW, Bowen-Pope DF (1986) The biology of platelet-derived growth factor. Cell 46:155–169

    Google Scholar 

  26. Rubin K, Hansson GK, Ronnstrand L (1988) Induction of B-type receptors for platelet-derived growth factor in vascular inflammation: possible implications for development of vascular proliferative lesions. Lancet i:1353–1356

    Google Scholar 

  27. Sachinidis A, Locher R, Vetter W, Tatje D, Hoppe J (1990) Different effects of platelet-derived growth factor isoforms on rat vascular smooth muscle cells. J Biol Chem 265:10238–10243

    Google Scholar 

  28. Schultz G, Cipolla L, Whitehouse A, Eiferman R, Woost P, Jumblatt M (1992) Growth factors and corneal endothelial cells. Ill. Stimulation of adult human corneal endothelial cell mitosis in vitro by defined mitogenic agents. Cornea 11:20–27

    Google Scholar 

  29. Seifert RA, Hart CE, Phillips PE, Forstrom JW, Ross R, Murray MJ, Bowen-Pope DF (1989) Two different subunits associate to create isoform-specific platelet-derived growth factor receptors. J Biol Chem 264:8771–8778

    Google Scholar 

  30. Skuta GL, Parrish RK (1987) Wound healing in glaucoma filtering surgery. Surv Ophthalmol 32:149–170

    Google Scholar 

  31. Terracio L, Ronnstrand L, Tingström A (1988) Induction of platelet-derived growth factor receptor expression in smooth muscle cells and fibroblasts upon tissue culturing. J Cell Biol 107:1947–1957

    Google Scholar 

  32. Tripathi RC, Borisuth NSC, Tripathi BJ (1991) Growth factors in the aqueous humor and their therapeutic implications in glaucoma and anterior segment disorders of the human eye. Drug Dev Res 22:1–23

    Google Scholar 

  33. Tripathi RC, Li J, Chalam KV, Tripathi BJ (1996) Expression of growth factor mRNAs by human Tenon's capsule fibroblasts. Exp Eye Res 63:339–346

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of General Ophthalmology, University Eye Clinic Tübingen, Schleichstrasse 12, D-72076, Tübingen, Germany

    Marcus Knorr, Michael Völker, Peter Oliver Denk, Kerstin Wunderlich & Hans-Jürgen Thiel

Authors
  1. Marcus Knorr
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Völker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter Oliver Denk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kerstin Wunderlich
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hans-Jürgen Thiel
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Presented in part at the annual meeting of the Deutsche Ophthalmologische Gesellschaft, Mannheim, September 1996

Rights and permissions

Reprints and permissions

About this article

Cite this article

Knorr, M., Völker, M., Denk, P.O. et al. Proliferative response of cultured human tenon's capsule fibroblasts to platelet-derived growth factor isoforms. Graefe's Arch Clin Exp Ophthalmol 235, 667–671 (1997). https://doi.org/10.1007/BF00946945

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00946945

Keywords

Search

Navigation