Skip to main content
Log in

Transforming growth factor-alpha is a constant component of human tear fluid

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

Abstract

Growth factors are known as a family of polypeptides with powerful influences on angiogenesis, tumor growth and wound healing. Transforming growth factor-alpha (TGF-α) and epidermal growth factor (EGF) are structurally related peptides which bind to the same receptor, EGF-R, and also exert similar effects. EGF is a natural component of human tears, and ocular disease leads to decreased concentrations in tear fluid. Using a sensitive radioimmunoassay we investigated whether TGF-α is also to be considered a natural component of tear fluid and in which concentrations it occurs. All of 46 tear fluid samples from 24 volunteers contained TGF-α. The mean concentration was 161.4 pg TGF-α/ml (SD 11.6 pg). No statistically significant correlation was found between tear fluid flow and TGF-α concentration in the sample. However, the concentration of TGF-α in tear fluid decreased significantly with increasing total time of tear fluid collection (P = 0.002). TGF-α levels in samples collected from males (n=16) appeared to be higher (mean 247.0 pg/ml, SD 15.3 pg/ml) than in those from females (n=30; mean 180.0 pg/ml, SD 8.5 pg/ml; P = 0.05). No correlation was found between the age of the individuals and the concentration of TGF-α in their tear fluid. The findings show that TGF-α is, like EGF, a constant component of human tear fluid. The dependence of TGF-α concentration on tear fluid flow and the physiological importance of its presence for corneal integrity and ocular surface physiology, however, require further investigation.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Burstein NL (1987) Review: growth factor effects on corneal wound healing. J Pharmacol 1:263–277

    Google Scholar 

  2. Carpenter G, Wahl MI (1991) The epidermal growth factor family. In: Sporn I, Roberts AB (eds) Peptide growth factors and their receptors, I. Springer, New York Berlin Heidelberg, pp 69–171

    Google Scholar 

  3. Chard T (1990) An introduction to radioimmunoassay and related techniques. In: Burdon RH, Knippenberg PH van (eds) Laboratory techniques in biochemistry and molecular biology, 4th edn. Elsevier, Amsterdam, p 21

    Google Scholar 

  4. Coffey RJ, Derynck R, Wilcox JN, Bringman TS, Goustin AS, et al (1987) Production and autoinduction of transforming growth factor α in human keratinocytes. Nature 328:817–820

    Google Scholar 

  5. Coffey RJ, Goustin AS, Mangelsdorf Soderquist A, Shipley GD, Wolfshohl J (1987) Transforming growth factor α and β expression in human colon cancer lines: implication for an autocrine model. Cancer Res 47:4590–4594

    Google Scholar 

  6. Cohen S (1962) Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J Biol Chem 237:1555–1562

    Google Scholar 

  7. Daniele S, Frati L, Fiore C, Santoni G (1979) The effect of the epidermal growth factor (EGF) on the corneal epithelium in humans. Graefe's Arch Clin Exp Ophthalmol 210:159–165

    Google Scholar 

  8. Derynck R (1988) Transforming growth factor α. Cell 54:593–595

    Google Scholar 

  9. Derynck R, Goeddel DV, Ullrich A, Gutterman JU, Williams RD, et al (1987) Synthesis of messenger RNAs for transforming growth factors α and β and the epidermal growth factor receptor by human tumors. Cancer Res 47:707–712

    CAS  PubMed  Google Scholar 

  10. Kamiya Y, Ohmura E, Murakami H, Shizume K, Tsushima T, Demura H, Sakuma N (1993) Transforming growth factor-alpha activity in effusions: comparison of radioimmunoassay and radioreceptorassay. Life Sci 52(16):1381–1386

    Google Scholar 

  11. Kandarakis A, Page C, Kaufman HE (1984) The effect of epidermal growth factor on epithelial healing after penetrating keratoplasty in human eyes. Am J Ophthalmol 98:411–415

    Google Scholar 

  12. Laato M, Niinikoski J, Gerdin B, Lebel L (1986) Stimulation of wound healing by epidermal growth factor: a dose-dependent effect. Ann Surg 203:379–388

    Google Scholar 

  13. Luetteke NC, Qiu TH, Peiffer RL, Oliver P, Smith O, Lee DC (1993) TGF-α deficiency results in hair follicle and eye abnormalities in targeted and waved-1 mice. Cell 73:263–278

    Article  CAS  PubMed  Google Scholar 

  14. Mann GB, Fowler KJ, Gabriel A, Nice EC, Williams RL, Dunn AR (1993) Mice with a null mutation of the TGF-α gene have abnormal skin architecture, wavy hair, and curly whiskers and often develop corneal inflammation. Cell 73:249–261

    Article  CAS  PubMed  Google Scholar 

  15. Marquardt H, Hunkapiller MW, Hood LE, Todaro GJ (1984) Rat transforming growth factor type I: structure and relation to epidermal growth factor. Science 223:1079–1082

    Google Scholar 

  16. Nasim MM, Thomas DM, Alison MR, Filipe MI (1992) Transforming growth factor alpha expression in normal gastric mucosa, intestinal metaplasia, dysplasia and gastric carcinoma — an immunohistochemical study. Histopathology 20:339–343

    Google Scholar 

  17. Okamura K, Morimoto A, Hamanaka R, Ono M, Kohno K, Uchida Y, Kuwano M (1992) A model system for tumor angiogenesis: involvement of transforming growth factor-alpha in tube formation of human microvascular endothelial cells induced by esophageal cancer cells. Biochem Biophys Res Commun 186:1471–1479

    Google Scholar 

  18. Rabiasz GJ, Langdon SP, Bartlett JM, Crew AJ, Miller EP, Scott WN, Smyth JF, Miller WR (1992) Growth control by epidermal growth factor and transforming growth factor-alpha in human lung squamous carcinoma cells. Br J Cancer 66:254–259

    Google Scholar 

  19. Savage CR, Cohen S (1973) Proliferation of corneal epithelium induced by epidermal growth factor. Exp Eye Res 15:361–366

    Google Scholar 

  20. Schultz G, White M, Mitchell R, Brown G, Flynch J, et al (1987) Epithelial wound healing enhanced by transforming growth factor-α and vaccinia growth factor. Science 235:350–352

    Google Scholar 

  21. Schultz G, Chegini N, Grant M, Khaw P, MacKay S (1992) Effects of growth factors on corneal wound healing. Acta Ophthalmol Copenh [Suppl] 202:60–66

    Google Scholar 

  22. Schultz G, Khaw P Grant M, MacKay S, Chegini N, Setten GB van (1994) Corneal wound healing: role of EGF and TGF-α. Eye 8 (in press)

  23. Setten GB van (1990) Epidermal growth factor in human tear fluid: increased release but decreased concentrations during reflex tearing. Curr Eye Res 9:79–83

    Google Scholar 

  24. Setten GB van (1993) Growth factors in human tear fluid: current concepts and models. In: Miglior M, Bijsterveld OP, Spinelli D (eds) Proceedings of the Symposium on the Lacrimal System, Brussels, 23–24 May, 1992. Ghedini Editore, Milan, pp 79–84

    Google Scholar 

  25. Setten GB van, Tervo T, Tarkkanen A, Pesonen K, Viinikka L, Perheentupa J (1989) Epidermal growth factor is a constant component of human tear fluid. Graefe's Arch Clin Exp Ophthalmol 227:84–87

    Google Scholar 

  26. Setten GB van, Tervo K, Virtanen I, Tarkkanen A, Tervo T (1990) Immunohistochemical demonstration of epidermal growth factor in the lacrimal and submandibular glands of rats. Acta Ophthalmol (Copenh) 68:477–480

    Google Scholar 

  27. Setten GB van, Tervo T, Viinikka L, Pesonen K, Perheentupa J, Tarkkanen A (1991) Ocular disease leads to decreased concentrations of epidermal growth factor in the tear fluid. Curr Eye Res 10:523–527

    Google Scholar 

  28. Setten GB van, Tervo T, Viinikka L, Perheentupa J, Tarkkanen A (1991) Epidermal growth factor in human tear fluid: a minireview. Int Ophthalmol 15:359–362

    Google Scholar 

  29. Setten GB van, Schultz GS, Macauley SS (1994) Growth factors in human tear fluid and in lacrimal glands submitted

  30. Smith JM, Sporn MB, Roberts AB, Derynck R, Winkler ME, Gregory H (1985) Human transforming growth factor-alpha causes precocoious eyelid opening in the newborn mice. Nature 315:515–516

    Google Scholar 

  31. Stroobant P, Rice AP, Gullick WJ, Cheng DJ, Kerr IM, et al (1985) Purification and characterization of vaccinia virus growth factor. Cell 42:383–393

    Google Scholar 

  32. Todaro GJ, Rose TM, Spooner CE, Shoyab M, Plowman GD (1990) Cellular and viral ligands that interact with the EGF receptor. Semin Cancer Biol 1:257–263

    Google Scholar 

  33. Tripathi BJ, Kwait PS, Tripathi RC (1990) Corneal growth factors: a new generation of ophthalmic pharmaceuticals. Cornea 9:2–9

    Google Scholar 

  34. Winkler ME, O'Connor L, Winget M, Fendly B (1989) Epidermal growth factor and transforming growth factor a bind differently to the epidermal growth factor receptor. Biochem 28:6373–6378

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

van Setten, G., Schultz, G. & van Setten, G. Transforming growth factor-alpha is a constant component of human tear fluid. Graefe's Arch Clin Exp Ophthalmol 232, 523–526 (1994). https://doi.org/10.1007/BF00181994

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00181994

Keywords

Navigation