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Vol. 212, No. 6, 1998
Issue release date: November–December 1998
Ophthalmologica 1998:212:410–414
(DOI:10.1159/000027378)

Detection of Vascular Endothelial Growth Factor and Tumor Necrosis Factor Alpha in Epiretinal Membranes of Proliferative Diabetic Retinopathy, Proliferative Vitreoretinopathy and Macular Pucker

Armstrong D. · Augustin A.J. · Spengler R. · Al-Jada A. · Nickola T. · Grus F. · Koch F.
aDepartment of Clinical Laboratory Science and Pathology, University of Buffalo, N.Y., USA; bDepartment of Clinical Ophthalmology, University of Bonn, and cDepartment of Ophthalmology, University of Frankfurt, Germany

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Abstract

Purpose: To evaluate epiretinal membranes in proliferative eye disease for the presence of vascular endothelial growth factor (VEGF) and tumor necrosis factor α (TNF-α). Methods: Membranes were surgically removed from 66 patients with proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR) and macular pucker (MP). Cytokine concentrations were determined by ELISA (VEGF) and bioassay (TNF-α). Results: VEGF was detected in all 66 membranes investigated. The highest VEGF values were found in patients with type I diabetes (mean = 5,994 pg/mg protein). In patients with type II diabetes, the values were at a mean of 1,242 pg/mg protein. When coagulation therapy was performed for longer than 3 months prior to surgery, VEGF was significantly (p < 0.05) reduced. Intermediate levels of VEGF were found in PVR membranes (mean = 1,417 pg/mg protein). The lowest activity was found in MP (mean = 216 pg/mg protein). In contrast, TNF-α was present in 16 PDR membranes, 9 PVR membranes and 8 MP membranes. Conclusion: The presence of VEGF in all membranes investigated indicates that this cytokine plays an important role in angiogenesis in ischemic retinal disease and in membrane growth in proliferative disorders.



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References

  1. Peer T, Shweiki D, Itin A, Hemo I, Gnessin H, Keshet E: Hypoxia-induced expression of vascular endothelial growth factor by retinal cells in a common factor in neovascularizing ocular disease. Lab Invest 1995;72:638–645.
  2. Stone J, Itin A, Peer AT, Gnessin H, Chanling T, Keshet E: Development of retinal vasculature is mediated by hypoxia-induced vascular endothelial growth factor (VEGF) expression by neurologia. J Neurosci 1995;15:4738–4747.
  3. Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, Nguyen HV, Aiello LM, Ferrara N, King GL: Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal diseases. N Engl J Med 1994;331:1480–1487.
  4. Aiello LP, Northrup JM, Keyt BA, Takagi H, Iwamoto MA: Hypoxia regulation of vascular endothelial growth factor in retinal cells. Arch Ophthalmol 1995;113:1538–1544.
  5. Pournaras CJ: Retinal oxygen distribution: Its role in the physiopathology of vasoproliferative microangiopathies. Retina 1995;15:332–347.
  6. Armstrong D, Abdella N, Salman A, Miller N, Abdel-Rahman E, Bojanczyk M: Relationships of lipid peroxides to complications: Comparison with conventional laboratory test. J Diabetes Complications 1992;6:116–122.
  7. Gallou G, Ruelland A, Legras B, Maugendre D, Allannic H, Cloarec L: Plasma malondialdehyde in type 1 and type 2 diabetic patients. Clin Chim Acta 1993;214:227–234.
  8. Augustin AJ, Breipohl W, Boker T, Spitznas M: Increased lipid peroxide levels and myeloperoxidase activity in the vitreous of patients suffering from proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 1993;231:647–650.
  9. Böker T, Augustin AJ, Breipohl W, Lutz J, Spitznas M: Increased lipid peroxide level and myeloperoxidase activity in the vitreous of patients suffering from proliferative vitreoretinopathy. Graefes Arch Clin Exp Ophthalmol 1994;232:652–656.
  10. Ignatowski T, Spengler R: Tumor necrosis factor alpha: Presynaptic sensitivity is modified after antidepressant drug administration. Brain Res 1994;665:293–299.
  11. Amin RH, Frank RN, Kennedy A, Eliott D, Puklin JE, Abrams GW: Vascular endothelial growth factor is present in glial cells of the retina and optic nerve of human subjects with nonproliferative diabetic retinopathy. Invest Ophthalmol Vis Sci 1997;38:36–47.
  12. Limb GA, Chignell AH, Woon H, Green W, Cole CJ, Dumonde DC: Evidence of chronic inflammation in retina excised after relaxing retinotomy for anterior proliferative vitreoretinopathy. Graefes Arch Clin Exp Ophthalmol 1996;234:213–220.
  13. Kliffen M, Sharma HS, Mooy CM, Kerkvliet S, de Jong PTVM: Increased expression of angiogenic growth factors in age-related maculopathy. Br J Ophthalmol 1997;81:154–162.
  14. Kutty RK, Kutty G, Hooks JJ, Wiggert B, Naginneni CN: Transforming growth factor beta inhibits the cytokine-mediated expression of the inducible nitric oxide synthase mRNA in human retinal pigment epithelial cells. Biochem Biophys Res Commun 1995;215:386–393.
  15. Platts KE, Benson MT, Rennie IG, Sharrad RM, Rees RC: Cytokine modulation of adhesion molecule expression on human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 1995;36:2262–2269.
  16. Chung M, Taba K, Casella AMB, Spee C, Hinton DR, Ryan SJ: Tumor necrosis factor alpha (TNF-α) stimulates migration of human retinal pigment epithelial cells (RPE) in vitro (abstract). Invest Ophthalmol Vis Sci 1997;38:S671.
  17. Thieme H, Aiello LP, Takagi H, Ferrara N, King GL: Comparative analysis of vascular endothelial growth factor receptors on retinal and aortic vascular endothelial cells. Diabetes 1995;44:98–103.
  18. Tang S, Le-Ruppert KC, Gabel V-P: Proliferation and activation of vascular endothelial cells in epiretinal membranes from patients with proliferative diabetic retinopathy. Ger J Ophthalmol 1994;3:131–136.
  19. Michelson IC: The mode of development of the vascular system of the retina with some observations on its significance for certain retinal diseases. Trans Ophthalmol Soc UK 1948;68:137–148.
  20. Malecaze F, Clamens S, Simorre-Pinatel V, Mathis A, Chollet P, Farvard C, Bayard F, Plouet J: Detection of vascular endothelial growth factor messenger RNA and vascular endothelial growth factor-like activity in proliferative diabetic retinopathy. Arch Ophthalmol 1994;112:1476–1482.
  21. Foreman D, Williams G, Boulton ME, McLeod D: VEGF distribution in proliferative diabetic retinopathy (abstract). Invest Ophthalmol Vis Sci 1996;37:5973.
  22. Tanaka Y, Kitano S, Hori S, Kato S, Fumatsu H, Miura M, Yamasita T, Yamamoto T, Yamashita H: Correlation between vascular endothelial growth factor (VEGF) and retinopathy progression in diabetic patients (abstract). Invest Ophthalmol Vis Sci 1996;37:5792.
  23. Shima D, Adamis A, Ferrara N, Yeo K, Allende R, Folkman J, D’Amore P: Hypoxic induction of endothelial growth factors in retinal cells: Identification and characterization of vascular endothelial growth factor as the mitogen. Mol Med 1995;1:182–193.
  24. Hashimoto E, Ogita T, Nakaoka T, Matsuoka R, Takao A, Kira Y: Rapid induction of vascular endothelial growth factor expression by transient ischemia in rat heart. Am J Physiol 1994;36:H1948–H1954.
  25. Augustin AJ, Spitznas M, Koch F, Grus F, Böker T: Indicators of oxidative tissue damage and inflammatory activity in epiretinal membranes of proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR) and macular pucker (MP). Ger J Ophthalmol 1995;4:47–51.
  26. Kelly J: Cytokines and lung. Am Rev Respir Dis 1990;141:765–788.
  27. Larrick J, Kunkel S: The role of tumor necrosis factor and interleukin-1 in the immunoinflammatory response. Pharm Res 1988;5:129–139.

    External Resources

  28. Ellner SG, Strieter RM, Elner VM, Rollins BJ, Del Monte MA, Kunkel SL: Monocyte chemotactic protein gene expression by cytokine-treated human retinal pigment epithelial cells. Lav Invest 1991;64:819–825.
  29. Vaddi K, Nicolini FA, Mehta P, Mehta JL: Increased secretion of tumor necrosis factor alpha and interferon gamma by mononuclear leukocytes in patients with ischemic heart diseases. Circulation 1994;90:694–699.
  30. Kauffmann DJH, van Meurs JC, Mertens DAE, Peperkamp E, Master C, Gerritsen ME: Cytokines in vitreous humor: Interleukin-6 is elevated in proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci 1994;35:900–906.
  31. Limb GA, Little BC, Meager A, Ogilvie JA, Wolstencroft RA, Franks WA, Chignell AN, Dumonde DC: Cytokines in proliferative vitreoretinopathy. Eye 1991;5:686–693.

    External Resources

  32. Yoshimura N, Matsumoto M, Shimizu H, Mandai M, Hata Y, Ishibashi T: Photocoagulated human retinal pigment epithelial cells produce an inhibitor of vascular endothelial cell proliferation. Invest Ophthalmol Vis Sci 1995;36:1686–1691.
  33. Koolwijk P, Vanerck MGM, Devree WJA, Vermeer M, Weich HA, Hanemaaijer R, Vanhinsberg VWM: Cooperative effect of TNF-α, bFGF and VEGF on the formation of tubular structures of human microvascular endothelial cells in a fibrin matrix – Role of urokinase activity. J Cell Biol 1996;132:1177–1188.

    External Resources

  34. Frank S, Hubner G, Breier G, Longaker M, Greenhalgh D, Werner S: Regulation of vascular endothelial growth factor expression in cultured keratinocytes – Implications for normal and impaired wound healing. J Biol Chem 1995;270:12607–12613.
  35. Frater-Schroder M, Risau W, Hallmann R, Gautoschi P, Bohlen P: Tumor necrosis factor type a, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo. Proc Natl Acad Sci USA 1987;84:5277–5281.
  36. Moreau T, Coles A, Wing M, Issacs J, Hale G, Waldmann H, Compston A: Transient increase in symptoms associated with cytokine release in patients with multiple sclerosis. Brain 1996;119:225–237.


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