Abstract
Transferrin (TF) is the major transport protein involved in human iron metabolism. The expression of the cell-surface TF receptor is associated with cellular proliferation, the dominant feature of proliferative vitreoretinal disorders with traction retinal detachment. A total of 14 retinal membranes from patients with different clinical diagnoses contained immunoreactive TF. Expression of the cell-surface TF receptor was confirmed by a monoclonal anti-human TF-receptor antibody label in 11 of the 14 specimens. We developed a noncompetitive enzyme-linked immunosorbent assay (ELISA) for TF and found it to be a significant component of vitreal protein, with a level of 65.7 ± 33.9 mg/l. Vitreal TF as a major iron acceptor probably has a protective function, but its interaction with macrophages and its growth-promoting activity may subsequently stimulate the proliferation of fibroblasts and retinal pigment epithelial cells.
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Adams DO, Hamilton TA (1984) The cell biology of macrophage activation. Ann Rev Immunol 2:283–318
Akiya S (1981) Soluble proteins in the developing vitreous. Acta Soc Ophthalmol Jpn 85: 1887–1909
Barnes D, Sato G (1980) Methods for growth of cultured cells in serum-free medium. Anal Biochem 102:255–270
Bomford AB, Munro HN (1986) Transferrin and its receptor: their role in cell function. Hepatology 5:870–875
Boonstra A, Kijlstra A (1984) The identification of transferrin, an iron-binding protein in rabbit tears. Exp Eye Res 38:561–567
Campochiaro PA, Glaser BM (1985) Platelet-derived growth factor is chemotactic for human retinal pigment epithelial cells. Arch Ophthalmol 103:576–579
Coe JI (1977) Post-mortem chemistry of blood, cerebrospinal fluid, and vitreous humour. In: Tedeschi CG, Eckert WG, Tedeschi LG (eds) Forensic medicine, vol II, chap 45. Saunders, Philadelphia, pp 1033–1060
Dautry-Varsat A, Ciechanover A, Lodish HF (1983) pH and the recycling of transferrin during receptor-mediated endocytosis. Proc Natl Acad Sci USA 80:2258–2260
Davis RJ, Czech MP (1986) Regulation of transferrin receptor expression at the cell surface by insulin-like growth factors, epidermal growth factor and platelet-derived growth factor. EMBO J 5: 653–658
Dernouchamps JP, Vaerman JP, Michiels J, Heremans JF (1974) Le dosage des protéines de l'humeur aqueuse et du vitré chez le lapin. Ophthalmologica 168: 132–139
Ekblom P, Thesleff I, Lehto VK (1983) Distribution of the transferrin receptor in normal human fibroblasts and fibrosarcoma cells. Int J Cancer 31:111–117
Freundlich B, Avdalovic N (1983) Use of gelatin/plasma coated flasks for isolating human peripheral blood monocytes. J Immunol Methods 62:31–37
Haller Yeo J, Sadeghi J, Campochiaro PA, Green R, Glaser BM (1986) Intravitreous fibronectin and platelet-derived growth factor. New model for traction retinal detachment. Arch Ophthalmol 104:417–421
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
Hawkins KN (1986) Contribution of plasma proteins to the vitreous of the rat. Curr Eye Res 5:655–663
Hilton G, Machemer R, Michels R, Okun E, Schepens CH, Schwartz A (1983) The classification of retinal detachment with proliferative vitreoretinopathy. Ophthalmology 90:121–125
Hiscott PS, Grierson I, McLeod D (1985) Natural history of fibrocellular epiretinal membranes: a quantitative, autoradiographic, and immunohistochemical study. Br J Ophthalmol 69: 810–823
Kampik A, Kenyon KR, Michels RG, Green WR, de la Cruz ZC (1981) Epiretinal and vitreous membranes. Arch Ophthalmol 99:1445–1454
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685
Larrick JL, Cresswell P (1979) Modulation of cell surface iron transferrin receptors by cellular density and state of activation. J Supramol Struct 11:579–586
Lesley JF, Schulte RJ (1985) Inhibition of cell growth by monoclonal anti-transferrin receptor antibodies. Mol Cell Biol 5:1814–1821
McGahan MC, Fleisher LN (1988) Inflammation-induced changes in the iron concentration and total iron-binding capacity of the intraocular fluids of rabbits. Graefe's Arch Clin Exp Ophthalmol 226: 27–30
Miller B, Miller H, Ryan SJ (1986) Experimental epiretinal proliferation induced by intravitreal red blood cells. Am J Ophthalmol 102:188–195
Miskimins WK, McClelland A, Roberts MP, Ruddle FH (1986) Cell proliferation and expression of the transferrin receptor gene: promoter sequence homologies and protein interactions. J Cell Biol 103:1781–1788
Nishisato T, Aisen P (1982) Uptake of transferrin by rat peritoneal macrophages. Br J Haematol 52:631–640
Omary MB, Trowbridge IS, Minowada J (1980) Human cell-surface glycoprotein with unusual properties. Nature 286:888–891
Penhallow RC, Brown-Mason A, Woodworth RC (1986) Comparative studies of the binding and growth-supportive ability of mammalian transferrins in human cells. J Cell Physiol 128: 251–260
Saito K, Nishisato T, Grasso JA, Aisen P (1986) Interaction of transferrin with iron-loaded rat peritoneal macrophages. Br J Haematol 62:275–286
Seppa H, Grotendorst G, Seppa S, Schiffman E, Martin GR (1982) Platelet-derived growth factor is chemotactic for fibroblasts. J Cell Biol 92:584–588
Towbin H, Gordon J (1984) Immunoblotting and dot immunobinding — current status and outlook. J Immunol Methods 72:313–340
Trowbridge IS, Lopez F (1982) Monoclonal antibody to transferrin receptor blocks transferrin binding and inhibits human tumor cell growth in vitro. Proc Natl Acad Sci USA 79:1175–1179
Trowbridge IS, Omary MB (1981) Human cell surface glycoprotein related to cell proliferation is the receptor for transferrin. Proc Natl Acad Sci USA 78:3039–3043
Van Bockxmeer FM, Martin CE, Constable IJ (1983) Iron-binding proteins in vitreous humour. Biochim Biophys Acta 758:17–23
Vernet-Nyssen M, Paris M, Benoit MO (1984) Are usual immunochemical methods for the determination of human serum transferrin influenced by the iron-saturation of the protein? Clin Chim Acta 143:355–360
Weller M, Heimann K, Wiedemann P (1988) Immunochemical studies of epiretinal membranes using APAAP complexes — evidence for macrophage involvement in traumatic proliferative vitreoretinopathy. Int Ophthalmol 11:181–186
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
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This study was supported by the Retinovit Foundation
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Weller, M., Wiedemann, P., Moter, H. et al. Transferrin and transferrin receptor expression in intraocular proliferative disease. APAAP-immunolabeling of retinal membranes and ELISA for vitreal transferrin. Graefe's Arch Clin Exp Ophthalmol 227, 281–286 (1989). https://doi.org/10.1007/BF02172763
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DOI: https://doi.org/10.1007/BF02172763