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Immunohistochemical localization of epidermal growth factor receptor in a human epiretinal membrane

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Abstract

Cell growth in proliferative vitreoretinopathy (PVR) is activated by naturally occurring mitogenic substances; thus, growth factors seem to play an important role in PVR. Cell activation by growth factors requires the presence of specific cell-bound receptors by which the mitogenic signal is transmitted. Using the indirect immunoperoxidase method, we investigated frozen sections of 15 epiretinal membranes in PVR for the presence of epidermal growth factor receptor (EGFR), which is commonly utilized by epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha). This receptor could be localized only in one epiretinal membrane. The receptor-bearing cells stained positively for vimentin, cytokeratin, and macrophage marker Ki-M7, indicating that they most probably correspond to transformed macrophages. They stained negatively for desmin and glial fibrillary acidic protein. The cells were embedded in a fibronectin-positive intercellular matrix and were in an actively proliferating state as demonstrated by positive staining for the nuclear proliferation marker Ki-67. We propose that EGFR might be expressed only in certain as yet undefined stages of PVR.

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References

  1. Berridge MJ (1986) Inositol lipids and cell proliferation. In: Kahn P, Graf Th (eds) Oncogenes and growth control. Springer, Berlin Heidelberg New York, pp 147–153

    Google Scholar 

  2. Burke JM, Twining SS (1987) Vitreous macrophage elicitation: generations of stimulants for pigment epithelium in vitro. Invest Ophthalmol Vis Sci 28:1100–1107

    Google Scholar 

  3. Campochiaro PA, Glaser BM (1985) Platelet-derived growth factor is chemotactic for human retinal pigment epithelial cells. Arch Ophthalmol 103:576–579

    Google Scholar 

  4. Campochiaro PA, Jerdan JA, Glaser BM, Cardin A, Michels RG (1985) Vitreous aspirates from patients with proliferative vitreoretinopathy stimulate retinal pigment epithelial cell migration. Arch Ophthalmol 103:1403–1405

    Google Scholar 

  5. Carpenter G, Cohen S (1976) [125I]-labeled human epidermal growth factor (hEGF): binding, internalization, and degradation in human fibroblasts. J Cell Biol 71:159–171

    Google Scholar 

  6. Carpenter G, Goodman L, Shaver L (1986) The physiology of epidermal growth factor. In: Kahn P, Graf Th (eds) Oncogenes and growth control. Springer, Berlin Heidelberg New York, pp 65–69

    Google Scholar 

  7. Caselitz J, Weber W, Seifert G (1986) Morphologische Untersuchungen des epidermalen Wachstumsfaktorrezeptor. Studien an menschlichen Tumoren und Tumortransplantaten auf athymische Mäuse mit besonderer Berücksichtigung von Speichel-drüsentumoren. (Morphological investigation of the epidermal growth factor receptor. Analysis of human tumors and tumor transplants in athymic mice, with special reference to salivary gland tumors.) Verh Dtsch Ges Pathol 70:343–346

    Google Scholar 

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

    Google Scholar 

  9. Couch JM, Cullen P, Casey TA, Fabre JW (1987) Mitotic activity of corneal endothelial cells in organ culture with recombinant human epidermal growth factor. Ophthalmology 94:1–6

    Google Scholar 

  10. Couch JM, Cullen P, Casey T, Fabre J (1988) Epidermal growth factor receptor sites in the human and monkey eye (abstr). Invest Ophthalmol Vis Sci 29 [Suppl]:86

    Google Scholar 

  11. Derynck R (1986) Transforming growth factor-alpha. In: Kahn P, Graf Th (eds) Oncogenes and growth control. Springer, Berlin Heidelberg New York, pp 58–64

    Google Scholar 

  12. Frati L, Daniele S, Delogu A, Covelli I (1972) Selective binding of the epidermal growth factor and its specific effects on the epithelial cells of the cornea. Exp Eye Res 14:135–141

    Google Scholar 

  13. Gerdes J, Schwab U, Lemke H, Stein H (1983) Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 31:13–20

    Google Scholar 

  14. Gerdes J, Lemke H, Baisch H, Wacker H-H, Schwab U, Stein H (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133:1710–1715

    Google Scholar 

  15. Gusterson B, Cowley G, Smith JA, Ozanne B (1984) Cellular localization of human epidermal growth factor receptor. Cell Biol Int Rep 8:649–657

    Google Scholar 

  16. Harvey AK, Roberge F, Hjelmeland LM (1987) Chemotaxis of rat retinal glia to growth factors found in repairing wounds. Invest Ophthalmol Vis Sci 28:1092–1099

    Google Scholar 

  17. Hiscott PS, Grierson I, McLeod D (1984) Retinal pigment epithelial cells in epiretinal membranes: an immunohistochemical study. Br J Ophthalmol 68:708–715

    Google Scholar 

  18. Ho PC, Davis WH, Elliott JH, Cohen S (1974) Kinetics of corneal epithelial regeneration and epidermal growth factor. Invest Ophthalmol Vis Sci 13:804–809

    Google Scholar 

  19. Hui YN, Goodnight R, Zhang XJ, Sorgente N, Ryan J (1988) Glial epiretinal membranes and contraction. Immnnohistochemical and morphological studies. Arch Ophthalmol 106:1280–1285

    Google Scholar 

  20. Kampik A, Kenyon KR, Michels RG, Green WR, Cruz ZC de la (1981) Epiretinal and vitreous membranes. Comparative study of 56 cases. Arch Ophthalmol 99:1445–1454

    Google Scholar 

  21. Kirchhof B, Kirchhof E, Ryan SJ, Dixon JFP, Barton BE, Sorgente N (1989) Macrophage modulation of retinal pigment epithelial cell migration and proliferation. Graefe's Arch Clin Exp Ophthalmol 227:60–66

    Google Scholar 

  22. Massague J (1983) Epidermal growth factor-like transforming growth factor: II. Interactions with epidermal growth factor receptors in human placenta membranes and A431 cells. J Biol Chem 258:13614–13620

    Google Scholar 

  23. Miller B, Miller H, Patterson R, Ryan SJ (1986) Retinal wound healing. Cellular activity at the vitreoretinal interface. Arch Ophthalmol 104:281–285

    Google Scholar 

  24. Nishida T, Nakamura M, Mishima H, Otori T (1990) Kinetics of stimulatory action of fibronectin and EGF on corneal epithelial migration (abstr). Invest Ophthalmol Vis Sci 31 [Suppl 4]:54

    Google Scholar 

  25. Rappolee DA, Mark D, Banda MJ, Werb Z (1988) Wound macrophages express TGF-alpha and other growth factors in vivo: analysis by mRNA phenotyping. Science 241:708–711

    Google Scholar 

  26. Rowen SL, Glaser BM (1985) Retinal pigment epithelial cells release a chemoattractant for astrocytes. Arch Ophthalmol 103:704–707

    Google Scholar 

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

    Google Scholar 

  28. Schreiber AB, Winkler ME, Derynck R (1986) Transforming growth factor-a is a more potent angiogenic mediator than epidermal growth factor. Science 232:1250–1253

    Google Scholar 

  29. Vinores SA, Campochiaro PA, Conway BP (1990) Ultrastructural and electron-immunocytochemical characterization of cells in epiretinal membranes. Invest Ophthalmol Vis Sci 31:14–28

    Google Scholar 

  30. Weller M, Heimann K, Wiedemann P (1988) Demonstration of mononuclear phagocytes in a human epiretinal membrane using a monoclonal anti-human macrophage antibody. Graefe's Arch Clin Exp Ophthalmol 226:252–254

    Google Scholar 

  31. Weller M, Wiedemann P, Heimann K, Zilles K (1988) The significance of fibronectin in vitreoretinal pathology. A critical evaluation. Graefe's Arch Clin Exp Ophthalmol 226:294–298

    Google Scholar 

  32. Wiedemann P, Ryan SJ, Novar P, Sorgente N (1985) Vitreous stimulates proliferation of fibroblasts and retinal pigment epithelial cells. Exp Eye Res 41:619–628

    Google Scholar 

  33. Yamashita H, Hori S, Masuda K (1986) Population and proportion of component cells in preretinal membranes. Jpn J Ophthalmol 30:269–281

    Google Scholar 

  34. Zhu Z-R, Begg IS, Palcic B (1990) Macrophage modulatio of fibroblast migration and proliferation in vitro (abstr). Invest Ophthalmol Vis Sci 31 [Suppl 4]:443

    Google Scholar 

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Heidenkummer, HP., Kampik, A. Immunohistochemical localization of epidermal growth factor receptor in a human epiretinal membrane. Graefe's Arch Clin Exp Ophthalmol 229, 492–496 (1991). https://doi.org/10.1007/BF00166316

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  • DOI: https://doi.org/10.1007/BF00166316

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