Parakrine Faktoren bei der diabetischen Retinopathie

  • Joachim Spranger
  • Uta Wegewitz
  • Andreas F. H. Pfeiffer
Part of the Molekulare Medizin book series (MOLMED)


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4.2.5 Literatur

  1. Aiello LP, Avery RL, Arigg PG et al. (1994) Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 331: 1480–1487PubMedCrossRefGoogle Scholar
  2. Aiello LP, Pierce EA, Foley ED et al. (1995) Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl Acad Sci USA 92: 10457–10461PubMedCrossRefGoogle Scholar
  3. Aiello LP, Bursell SE, Clermont A et al. (1997) Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor. Diabetes 46: 1473–1480PubMedGoogle Scholar
  4. Aiello LP, Gardner TW, King GL et al. (1998) Diabetic retinopathy. Diabetes Care 21(1): 143–156PubMedGoogle Scholar
  5. Antonelli-Orlidge A, Saunders KB, Smith SR and D’Amore PA (1989) An activated form of transforming growth factor beta is produced by cocultures of endothelial cells and pericytes. Proc Natl Acad Sci USA 86(12): 4544–4548PubMedCrossRefGoogle Scholar
  6. Bainbridge JW, Mistry A, De Alwis M et al. (2002) Inhibition of retinal neovascularisation by gene transfer of soluble VEGF receptor sFlt-1. Gene Ther 9(5): 320–326PubMedCrossRefGoogle Scholar
  7. Bainbridge JW, Mistry AR, Thrasher AJ, Ali RR (2003) Gene therapy for ocular angiogenesis. Clin Sci (Lond) 104(6): 561–575PubMedCrossRefGoogle Scholar
  8. Baird A, Culler F, Jones K (1985 a) Angiogenic factor in human ocular fluid. Brit Med J 2: 563Google Scholar
  9. Baird A, Esch F, Gospodarowicz D, Guillemin R (1985b) Retina-and eye-derived endothelial cell growth factors: partial molecular characterization and identity with acidic and basic fibroblast growth factors. Biochemistry 24(27): 7855–7860PubMedCrossRefGoogle Scholar
  10. Bensaid M, Malecaze F, Prats H, Bayard F, Tauber JP (1989) Autocrine regulation of bovine retinal capillary endothelial cell (BREC) proliferation by BREC-derived basic fibroblast growth factor. Exp Eye Res 48(6): 801–813PubMedCrossRefGoogle Scholar
  11. Boehm BO, Lustig RH (2002) Use of somatostatin receptor ligands in obesity and diabetic complications. Best Pract Res Clin Gastroenterol 16(3): 493–509PubMedCrossRefGoogle Scholar
  12. Boehm BO, Lang GK, Jehle PM, Feldman B, Lang GE (2001) Octreotide reduces vitreous hemorrhage and loss of visual acuity risk in patients with high-risk proliferative diabetic retinopathy. Horm Metab Res 33(5): 300–306PubMedCrossRefGoogle Scholar
  13. Boehm BO, Lang G, Volpert O et al. (2003) Low content of the natural ocular anti-angiogenic agent pigment epithelium-derived factor (PEDF) in aqueous humor predicts progression of diabetic retinopathy. Diabetologia 46(3): 394–400PubMedGoogle Scholar
  14. Borras T (2003) Recent developments in ocular gene therapy. Exp Eye Res 76(6): 643–652PubMedCrossRefGoogle Scholar
  15. Brown PD, Wakefield LM, Levinson AD, Sporn MB (1990) Physicochemical activation of recombinant latent transforming growth factor-beta’s 1, 2, and 3. Growth factors 3(1): 35–43PubMedGoogle Scholar
  16. Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414(6865): 813–820PubMedCrossRefGoogle Scholar
  17. Brownlee M, Cerami A, Vlassara H (1988) Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med 318: 1315–1321PubMedCrossRefGoogle Scholar
  18. Bursell SE, Takagi C, Clermont AC et al. (1997) Specific retinal diacylglycerol and protein kinase C beta isoform modulation mimics abnormal retinal hemodynamics in diabetic rats. Invest Ophthalmol Vis Sci 38(13): 2711–2720PubMedGoogle Scholar
  19. Campochiaro PA (2004) Reduction of diabetic macular edema by oral administration of the kinase inhibitor PKC412. Invest Ophthalmol Vis Sci 45(3): 922–931PubMedCrossRefGoogle Scholar
  20. Chaturvedi N, Sjolie AK, Stephenson JM et al. (1998) Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes. The EUCLID Study Group. EURODIAB Controlled Trial of Lisinopril in Insulin-Dependent Diabetes Mellitus. Lancet 351(9095): 28–31PubMedCrossRefGoogle Scholar
  21. Davidson JM, Klagsbrun M, Hill KE et al. (1985) Accelerated wound repair, cell proliferation, and collagen accumulation are produced by a cartilage-derived growth factor. J Cell Biol 100(4): 1219–1227PubMedCrossRefGoogle Scholar
  22. Dawson DW, Volpert OV, Gillis P et al. (1999) Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science 285(5425): 245–248PubMedCrossRefGoogle Scholar
  23. DCCT-Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329(14): 977–986CrossRefGoogle Scholar
  24. DCCT-Research Group (1998) Early worsening of diabetic retinopathy in the Diabetes Control and Complications Trial. Arch Ophthalmol 116: 874–886Google Scholar
  25. EYETECH Study Group (2002) Preclinical and phase 1A clinical evaluation of an anti-VEGF pegylated aptamer (EYE001) for the treatment of exudative age-related macular degeneration. Retina 22(2): 143–152Google Scholar
  26. EYETECH Study Group (2003) Anti-vascular endothelial growth factor therapy for subfoveal choroidal neovascularization secondary to age-related macular degeneration: phase II study results. Ophthalmology 110(5): 979–986CrossRefGoogle Scholar
  27. Ferrara N (1999) Vascular endothelial growth factor: molecular and biological aspects. Curr Top Microbiol Immunol 237: 1–30PubMedGoogle Scholar
  28. Frank RN (2002) Potential new medical therapies for diabetic retinopathy: protein kinase C inhibitors. Am J Ophthalmol 133(5): 693–698PubMedCrossRefGoogle Scholar
  29. Fredj-Reygrobellet D, Baudouin C, Negre F, Caruelle JP, Gastaud P, Lapalus P (1991) Acidic FGF and other growth factors in preretinal membranes from patients with diabetic retinopathy and proliferative vitreoretinopathy. Ophthalmic Res 23(3): 154–161PubMedCrossRefGoogle Scholar
  30. Gall MA, Rossing P, Skott P et al. (1991) Prevalence of micro-and macroalbuminuria, arterial hypertension, retinopathy and large vessel disease in European type 2 (non-insulin-dependent) diabetic patients. Diabetologia 34(9): 655–661PubMedCrossRefGoogle Scholar
  31. Garcia de la Torre N, Wass JA, Turner HE (2002) Antiangiogenic effects of somatostatin analogues. Clin Endocrinol (Oxf) 57(4): 425–441CrossRefGoogle Scholar
  32. Giardino I, Edelstein D, Brownlee M (1994) Nonenzymatic glycosylation in vitro and in bovine endothelial cells alters basic fibroblast growth factor activity. A model for intracellular glycosylation in diabetes. J Clin Invest 94(1): 110–117PubMedGoogle Scholar
  33. Glaser BM, D’Amore PA, Michels RG, Patz A, Fenselau A (1980) Demonstration of vasoproliferative activity from mammalian retina. J Cell Biol 84(2): 298–304PubMedCrossRefGoogle Scholar
  34. Grant MB, Caballero S (2002) Somatostatin analogues as drug therapies for retinopathies. Drugs Today (Barc) 38(11): 783–791CrossRefPubMedGoogle Scholar
  35. Grant MB, Mames RN, Fitzgerald C et al. (2000) The efficacy of octreotide in the therapy of severe nonproliferative and early proliferative diabetic retinopathy: a randomized controlled study. Diabetes Care 23(4): 504–509PubMedGoogle Scholar
  36. Growth Hormone Antagonist For Proliferative Diabetic Retinopathy Study Group (2001) The effect of a growth hormone receptor antagonist drug on proliferative diabetic retinopathy. Ophthalmology 108(12): 2266–2272CrossRefGoogle Scholar
  37. Hanneken A, de-Juan E Jr, Lutty GA, Fox GM, Schiffer S, Hjelmeland LM (1991) Altered distribution of basic fibro-blast growth factor in diabetic retinopathy. Arch Ophthalmol 109(7): 1005–1011PubMedGoogle Scholar
  38. Hearn MT (1991) Structure and function of the heparin-binding (fibroblast) growth factor family. Baillieres. Clin Endocrinol Metab 5(4): 571–593Google Scholar
  39. Hyer SL, Sharp PS, Brooks RA, Burrin JM, Kohner EM (1989 a) Continuous subcutaneous octreotide infusion markedly suppresses IGF-I levels whilst only partially suppressing GH secretion in diabetics with retinopathy. Acta Endocrinol (Copenh) 120(2): 187–194PubMedGoogle Scholar
  40. Hyer SL, Sharp PS, Burrin JM, Kohner EM (1989b) Progression of diabetic retinopathy and changes in serum insulin-like growth factor I (IGF-I) during continous subcutaneous insulin infusion. Horm Metab Res 21: 18–22PubMedGoogle Scholar
  41. Jennings JC, Mohan S, Linkhart TA, Widstrom R, Baylink DJ (1988) Comparison of the biological actions of TGF beta-1 and TGF beta-2: differential activity in endothelial cells. J Cell Physiol 137(1): 167–172PubMedCrossRefGoogle Scholar
  42. Kirkegaard C, Norgaard K, Snorgaard O, Bek T, Larsen M, Lund Andersen H (1990) Effect of one year continuous subcutaneous infusion of a somatostatin analogue, octreotide, on early retinopathy, metabolic control and thyroid function in type I (insulin dependent) diabetes mellitus. Acta Endocrinol 122: 766–772PubMedGoogle Scholar
  43. Klein R, Klein BE, Moss SE, Davis MD, DeMets DL (1984) The Wisconsin epidemiologic study of diabetic retinopathy. III. Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years. Arch Ophthalmol 102(4): 527–532PubMedGoogle Scholar
  44. Koya D, Jirousek MR, Lin YW, Ishii H, Kuboki K, King GL (1997) Characterization of protein kinase C beta isoform activation on the gene expression of transforming growth factor-beta, extracellular matrix components, and prostanoids in the glomeruli of diabetic rats. J Clin Invest 100(1): 115–126PubMedCrossRefGoogle Scholar
  45. Krzystolik MG, Afshari MA, Adamis AP et al. (2002) Prevention of experimental choroidal neovascularization with intravitreal anti-vascular endothelial growth factor anti-body fragment. Arch Ophthalmol 120(3): 338–346PubMedGoogle Scholar
  46. Kuijpers RW, Baarsma S, van Hagen PM (1998) Treatment of cystoid macular edema with octreotide. N Engl J Med 338(9): 624–626PubMedCrossRefGoogle Scholar
  47. Lai CC, Wu WC, Chen SL et al. (2001) Suppression of choroidal neovascularization by adeno-associated virus vector expressing angiostatin. Invest Ophthalmol Vis Sci 42(10): 2401–2407PubMedGoogle Scholar
  48. Lai YK, Shen WY, Brankov M, Lai CM, Constable IJ, Rakoczy PE (2002) Potential long-term inhibition of ocular neovascularisation by recombinant adeno-associated virus-mediated secretion gene therapy. Gene Ther 9(12): 804–813PubMedCrossRefGoogle Scholar
  49. Lee HK, Suh KI, Koh CS, Min HK, Lee JH, Chung H (1988) Effect of SMS 201–995 in rapidly progressive diabetic retinopathy. Diabetes Care 11(5): 441–443PubMedGoogle Scholar
  50. Lyons RM, Gentry LE, Purchio AF, Moses HL (1990) Mechanism of activation of latent recombinant transforming growth factor beta 1 by plasmin. J Cell Biol 110(4): 1361–1367PubMedCrossRefGoogle Scholar
  51. Mallet B, Vialettes B, Haroche S et al. (1992) Stabilization of severe proliferative diabetic retinopathy by long-term treatment with SMS 201–995. Diabet Metab 18(6): 438–444Google Scholar
  52. McCombe M, Lightman S, Eckland DJ, Hamilton AM, Lightman SL (1991) Effect of a long-acting somatostatin analogue (BIM23014) on proliferative diabetic retinopathy: a pilot study. Eye 5 (Pt 5): 569–575PubMedGoogle Scholar
  53. Merimee TJ (1990) Diabetic retinopathy. N Engl J Med 322: 978–982PubMedCrossRefGoogle Scholar
  54. Milton R, Aiello L, Davis M, Sheetz M, Arora V, Vignati L (2003) Initial results of the Protein Kinase C b Inhibitor Diabetic Retinopathy Study (PKC-DRS). Diabetologia 46(Suppl 2): A42Google Scholar
  55. Miyazono K, Heldin CH (1989) Role for carbohydrate structures in TGF-beta 1 latency. J Exp Clin Endocrinol Diabet 338(6211): 158–160Google Scholar
  56. Montesano R, Vassalli JD, Baird A, Guillemin R, Orci L (1986) Basic fibroblast growth factor induces angiogenesis in vitro. Proc Natl Acad Sci USA 83(19): 7297–7301PubMedCrossRefGoogle Scholar
  57. Mori K, Ando A, Gehlbach P et al. (2001a) Inhibition of choroidal neovascularization by intravenous injection of adenoviral vectors expressing secretable endostatin. Am J Pathol 159(1): 313–320PubMedGoogle Scholar
  58. Mori K, Duh E, Gehlbach P et al. (2001b) Pigment epithelium-derived factor inhibits retinal and choroidal neovascularization. J Cell Physiol 188(2): 253–263PubMedCrossRefGoogle Scholar
  59. Mori K, Gehlbach P, Ando A, McVey D, Wei L, Campochiaro PA (2002 a) Regression of ocular neovascularization in response to increased expression of pigment epithelium-derived factor. Invest Ophthalmol Vis Sci 43(7): 2428–2434PubMedGoogle Scholar
  60. Mori K, Gehlbach P, Yamamoto S et al. (2002 b) AAV-mediated gene transfer of pigment epithelium-derived factor inhibits choroidal neovascularization. Invest Ophthalmol Vis Sci 43(6): 1994–2000PubMedGoogle Scholar
  61. Murata T, Cui J, Taba KE et al. (2000) The possibility of gene therapy for the treatment of choroidal neovascularization. Ophthalmology 107(7): 1364–1373PubMedCrossRefGoogle Scholar
  62. Nishikawa T, Edelstein D, Du XL et al. (2000) Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404(6779): 787–790PubMedCrossRefGoogle Scholar
  63. Pfeiffer A, Spranger J, Meyer-Schwickerath R, Schatz H (1997) Growth factor alterations in advanced diabetic retinopathy: a possible role of blood retina barrier break-down. Diabetes 46(Suppl 2): S26–30PubMedGoogle Scholar
  64. Pircher R, Lawrence DA, Jullien P (1984) Latent beta-transforming growth factor in nontransformed and Kirsten sarcoma virus-transformed normal rat kidney cells, clone 49F. Cancer Res 44 (12, Pt 1): 5538–5543PubMedGoogle Scholar
  65. Poulsen JD (1953) Diabetes and anterior pituitary deficiency. Diabetes 2: 7–12PubMedGoogle Scholar
  66. Raisler BJ, Berns KI, Grant MB, Beliaev D, Hauswirth W (2002) Adeno-associated virus type-2 expression of pigmented epithelium-derived factor or Kringles 1–3 of angiostatin reduce retinal neovascularization. Proc Natl Acad Sci USA 99(13): 8909–8914PubMedCrossRefGoogle Scholar
  67. Rasmussen H, Chu KW, Campochiaro P et al. (2001) Clinical protocol. An open-label, phase I, single administration, dose-escalation study of ADGVPEDF.11D (ADPEDF) in neovascular age-related macular degeneration (AMD). Hum Gene Ther 12(16): 2029–2032PubMedGoogle Scholar
  68. Reich SJ, Bennett J (2003) Gene therapy for ocular neovascularization: a cure in sight. Curr Opin Genet Dev 13(3): 317–322PubMedCrossRefGoogle Scholar
  69. Robinson GS, Pierce EA, Rook SL, Foley E, Webb R, Smith LE (1996) Oligodeoxynucleotides inhibit retinal neovas-cularization in a murine model of proliferative retinopathy. Proc Natl Acad Sci USA 93(10): 4851–4856PubMedCrossRefGoogle Scholar
  70. Sato Y, Rifkin DB (1989) Inhibition of endothelial cell movement by pericytes and smooth muscle cells: activation of a latent transforming growth factor-beta 1-like molecule by plasmin during co-culture. J Cell Biol 109(1): 309–315PubMedCrossRefGoogle Scholar
  71. Sharp PS (1995) Growth factors in the pathogenesis of diabetic retinopathy. Diabetes Rev 3: 164–176Google Scholar
  72. Sharp PS, Fallon TJ, Brazier J, Sandier LM, Joplin GF, Kohner EM (1987) Long term follow-up of patients who underwent yttrium-90 pituitary implantation for treatment of proliferative diabetic retinopathy. Diabetologia 30: 199–207PubMedCrossRefGoogle Scholar
  73. Sheetz MJ, King GL (2002) Molecular understanding of hyperglycemia’s adverse effects for diabetic complications. Jama 288(20): 2579–2588PubMedCrossRefGoogle Scholar
  74. Shing Y, Folkman J, Haudenschild C, Lund D, Crum R, Klagsbrun M (1985) Angiogenesis is stimulated by a tumor-derived endothelial cell growth factor. J Cell Biochem 29(4): 275–287PubMedCrossRefGoogle Scholar
  75. Shumak SL, Grossman LD, Chew E et al. (1990) Growth hormone suppression and nonproliferative diabetic retinopathy: a preliminary feasibility study. Clin Invest Med 13(5): 287–292PubMedGoogle Scholar
  76. Shweiki D, Itin A, Soffer D, Keshet E (1992) Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359(6398): 843–845PubMedCrossRefGoogle Scholar
  77. Singh R, Barden A, Mori T, Beilin L (2001) Advanced glycation end-products: a review. Diabetologia 44(2): 129–146PubMedCrossRefGoogle Scholar
  78. Sivalingam A, Kenney J, Brown GC, Benson WE, Donoso L (1990) Basic fibroblast growth factor levels in the vitreous of patients with proliferative diabetic retinopathy. Arch Ophthalmol 108(6): 869–872PubMedGoogle Scholar
  79. Smith LEH, Kopchick JJ, Chen W et al. (1997) Essential role of growth hormone in ischemia-induced retinal neovascularization. Science 276: 1706–1709PubMedCrossRefGoogle Scholar
  80. Smith LE, Shen W, Perruzi C et al. (1999) Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor. Nature 5: 1390–1395CrossRefGoogle Scholar
  81. Spranger J, Meyer-Schwickerath R, Klein M, Schatz H, Pfeiffer A (1999) Deficient activation and different expression of transforming growth factor-beta isoforms in active proliferative diabetic retinopathy and neovascular eye disease. Exp Clin Endocrinol Diabetes 107(1): 21–28PubMedCrossRefGoogle Scholar
  82. Spranger J, Bühnen J, Jansen V et al. (2000 a) Systemic levels contribute significantly to increased intraocular IGF-I, IGF-II and IGF-BP3 in proliferative diabetic retinopathy. Horm Metab Res 32(5): 196–200PubMedCrossRefGoogle Scholar
  83. Spranger J, Hammes HP, Preissner KT, Schatz H, Pfeiffer AF (2000 b) Release of the angiogenesis inhibitor angiostatin in patients with proliferative diabetic retinopathy: Association with retinal photocoagulation. Diabetologia 43(11): 1404–1407PubMedCrossRefGoogle Scholar
  84. Spranger J, Osterhoff M, Reimann M et al. (2001) Loss of the antiangiogenic pigment epithelium-derived factor in patients with angiogenic eye disease. Diabetes 50(12): 2641–2645PubMedGoogle Scholar
  85. Stellmach VV, Crawford SE, Zhou W, Bouck N (2001) Prevention of ischemia-induced retinopathy by the natural ocular antiangiogenic agent pigment epithelium-derived factor. Proc Natl Acad Sci USA 98(5): 2593–2597PubMedCrossRefGoogle Scholar
  86. Thomas KA (1987) Fibroblast growth factors. Faseb J 1(6): 434–440PubMedGoogle Scholar
  87. UKPDS-Group (1998 a) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Brit Med J 352: 837–853Google Scholar
  88. UKPDS-Group (1998 b) Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes (UKPDS 38). Brit Med J 317: 703–713Google Scholar
  89. Way KJ, Katai N, King GL (2001) Protein kinase C and the development of diabetic vascular complications. Diabet Med 18(12): 945–959PubMedCrossRefGoogle Scholar
  90. Williams B, Gallacher B, Patel H, Orme C (1997) Glucose-induced protein kinase C activation regulates vascular permeability factor mRNA expression and peptide production by human vascular smooth muscle cells in vitro. Diabetes 46(9): 1497–1503PubMedGoogle Scholar
  91. Witmer AN, Vrensen GF, Van Noorden CJ, Schlingemann RO (2003) Vascular endothelial growth factors and angiogenesis in eye disease. Prog Retin Eye Res 22(1): 1–29PubMedCrossRefGoogle Scholar
  92. Yang L, Berk SC, Rohrer SP et al. (1998) Synthesis and biological activities of potent peptidomimetics selective for somatostatin receptor subtype 2. Proc Natl Acad Sci USA 95(18): 10836–10841PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • Joachim Spranger
    • 1
    • 2
  • Uta Wegewitz
    • 1
  • Andreas F. H. Pfeiffer
    • 1
    • 3
  1. 1.Abteilung Klinische ErnährungDeutsches Institut für Ernährungsforschung PotsdamNuthetal
  2. 2.Campus Benjamin Franklin, Abteilung für Endokrinologie, Diabetes und ErnährungsmedizinCharité UniversitätsmedizinBerlin
  3. 3.Campus Benjamin Franklin Medizinische Klinik I Endokrinologie, Diabetes und ErnährungsmedizinUniversitätsmedizin BerlinBerlin

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