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Is Diabetic Retinopathy an Inflammatory Disease? Inflammation as a Stimulus for Vascular Leakage and Proliferati on

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Uveitis and Immunological Disorders

Part of the book series: Essentials in Ophthalmology ((ESSENTIALS))

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Diabetic macular edema is the most common cause of visual impairment in patients with diabetes mellitus, and it affects approximately 75,000 new patients in the United States every year [14, 65, 66]. The incidence of macular edema significantly increases with increasing severity of diabetes in both early-onset and late-onset diabetic patients [65, 66].

Diabetic macular edema tends to be a chronic disease. Although spontaneous recovery is not uncommon, 24% of eyes with clinically significant macular edema (CSME) and 33% of eyes with center-involving CSME will have a moderate visual loss (15 or more letters on the ETDRS chart) within three years if untreated [27, 31].

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References

  1. Adamis A P, Miller J W, Bernal MT, D'Amico DJ, Folkman J, Yeo TK, Yeo KT (1994) Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol 118:445–450

    PubMed  CAS  Google Scholar 

  2. Adamis A P, Altaweel M, Bressler NM, Cunningham ET Jr, Davis MD, Goldbaum M, Gonzales C, Guyer DR, Barrett K, Patel M, Macugen Diabetic Retinopathy Study Group (2006) Changes in retinal neovascularization after pegaptanib (Macugen) therapy in diabetic individuals. Ophthalmology 113:23–28

    Google Scholar 

  3. Aiello L P, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, Nguyen H V, Aiello LM, Ferrara N, King GL (1994) Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 331:1480–1487

    Article  PubMed  CAS  Google Scholar 

  4. Aiello L P, Northrup JM, Keyt BA, Takagi H, Iwamoto MA (1995) Hypoxic regulation of vascular endothelial growth factor in retinal cells. Arch Ophthalmol 113:1538–1544

    PubMed  CAS  Google Scholar 

  5. Alon T, Hemo I, Itin A, Pe'er J, Stone J, Keshet E (1995) Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med 1:1024–1028

    Article  PubMed  CAS  Google Scholar 

  6. Antcliff RJ, Spalton DJ, Stanford MR, Graham EM, Ffytche TJ, Marshall J (2001) Intravitreal triamcinolone for uveitic cystoid macular edema: an optical coherence tomography study. Ophthalmology 108:765–772

    Article  PubMed  CAS  Google Scholar 

  7. Antonetti D, Barber AJ, Hollinger LA, Wolpert EB, Gardner TW (1999) Vascular endothelial growth factor induces rapid phosphorylation of tight junction proteins occludin and zonula occluden 1. J Biol Chem 274:23463–23467

    Article  PubMed  CAS  Google Scholar 

  8. Antonetti DA, Wolpert EB, DeMaio L, Harhaj NS, Scaduto RC Jr (2002) Hydrocortisone decreases retinal endothelial cell water and solute flux coincident with increased content and decreased phosphorylation of occludin. J Neurochem 80:667–677

    Article  PubMed  CAS  Google Scholar 

  9. Asahara T, Takahashi T, MasudaH, Kalka C, Chen D, Iwaguro H, Inai Y, Silver M, Isner JM (1999) VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 18:3964–3972

    Article  PubMed  CAS  Google Scholar 

  10. Avery RL, Pearlman J, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, Giust MJ, Wendel R, Patel A (2006) Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology 113(10;1695):E1–E15

    PubMed  Google Scholar 

  11. Barleon B, Sozzani S, Zhou D, Weich HA, Mantovani A, Marme D (1996) Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. Blood 87:3336–3343

    PubMed  CAS  Google Scholar 

  12. Blaauwgeers HG, Holtkamp GM, Rutten H, Witmer AN, Koolwijk P, Partanen TA, et al. (1999) Polarized vascular endothelial growth factor secretion by human retinal pigment epithelium and localization of vascular endothelial growth factor receptors on the inner choriocapillaris. Evidence for a trophic paracrine relation. Am J Pathol 155:421–428

    PubMed  CAS  Google Scholar 

  13. Boeri D, Cagliero E, Podesta F, Lorenzi M (1994) Vascular wall von Willebrand factor in human diabetic retinopathy. Invest Ophthalmol Vis Sci 35:600–607

    PubMed  CAS  Google Scholar 

  14. Bresnick GH (1986) Diabetic macular edema. A review. Ophthalmology 93:989–997

    CAS  Google Scholar 

  15. Brooks HL Jr, Caballero S Jr, Newell CK, Steinmetz RL, Watson D, Segal MS, Harrison JK, Scott E W, Grant MB (2004) Vitreous levels of vascular endothelial growth factor and stromal-derived factor 1 in patients with diabetic retinopathy and cystoid macular edema before and after intraocular injection of triamcinolone. Arch Ophthalmol 122:1801–1807

    Article  PubMed  CAS  Google Scholar 

  16. Brown PO, Botstein D (1999) Exploring the new world of the genome with DNA microarrays. Nat Genet 21:S33–S37

    Article  Google Scholar 

  17. Caldwell RB, Bartoli M, Behzadian MA, El-Remessy AE, Al-Shabrawey M, Platt DH, Caldwell RW (2003) Vascular endothelial growth factor and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives. Diabetes Metab Res Rev 19:442–455

    Article  PubMed  CAS  Google Scholar 

  18. Chen E, Park CH (2006) Use of intravitreal bevacizumab as a preoperative adjunct for tractional retinal detachment repair in severe proliferative diabetic retinopathy. Retina 26:699–700

    Article  PubMed  Google Scholar 

  19. Clauss M, Gerlach M, Gerlach H, Brett J, Wang F, Familletti PC, Pan YC, Olander J V, Connolly DT, Stern D (1990) Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. J Exp Med 172:1535–1545

    Article  PubMed  CAS  Google Scholar 

  20. Comer GM, Ciulla TA (2004) Pharmacotherapy for diabetic retinopathy. Curr Opin Ophthalmol 15:508–518

    Article  PubMed  Google Scholar 

  21. Diabetic Retinopathy Clinical Research Network (2007) A phase 2 randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthalmology 114:1860–1867

    Article  Google Scholar 

  22. Cunningham ET Jr, Adamis A P, Altaweel M, Aiello LP, Bressler NM, D'Amico DJ, Goldbaum M, Guyer DR, Katz B, Patel M, Schwartz SD, Macugen Diabetic Retinopathy Study Group (2005) A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema. Ophthalmology 112:1747–1757

    Google Scholar 

  23. Dick AD (1994) The treatment of chronic uveitic macular edema. Br J Ophthalmol 78:1–2

    Article  PubMed  CAS  Google Scholar 

  24. Duggan DJ, Bittner M, Chen Y, Meltzer P, Trent JM (1999) Expression profiling using cDNA microarrays. Nat Genet 21:S10–S14

    Article  Google Scholar 

  25. Engerman RL, Kern TS (1995) Retinopathy in galactosemic dogs continues to progress after cessation of galactosemia. Arch Ophthalmol 113:355–358

    PubMed  CAS  Google Scholar 

  26. Espinosa-Heidmann DG, Suner IJ, Hernandez E P, Monroy D, Csaky KG, Cousins SW (2003) Macrophage depletion diminishes lesion size and severity in experimental choroidal neovascularization. Invest Ophthalmol Vis Sci 44: 3586–3592

    Article  Google Scholar 

  27. Early Treatment Diabetic Retinopathy Study Research Group (1985) Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study Report Number 1. Arch Ophthalmol 103:1796–1806

    Google Scholar 

  28. ETDRS Investigators (1992) Aspirin effects on mortality and morbidity in patients with diabetes mellitus. ETDRS Report No. 14. JAMA 268:1292–1300

    Google Scholar 

  29. Famiglietti EV, Stopa EG, McGookin ED, Song P, LeBlanc V, Streeten BW (2003) Immunocytochemical localization of vascular endothelial growth factor in neurons and glial cells of human retina. Brain Res 969:195–204

    Article  PubMed  CAS  Google Scholar 

  30. Ferrara N (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25:581–611

    Article  PubMed  CAS  Google Scholar 

  31. Ferris FL 3rd, Patz A (1984) Macular edema. A complication of diabetic retinopathy. Surv Ophthalmol 28(Suppl):452–461

    Google Scholar 

  32. Fong DS, Aiello L P, Ferris FL 3rd, Klein R (2004) Diabetic retinopathy. Diabetes Care 27:2540–2553

    Article  PubMed  Google Scholar 

  33. Franks WA , Limb GA, Stanford MR, Ogilvie J, Wolstencroft RA, Chignell AH, Dumonde DC (1992) Cytokines in human intraocular inflammation. Curr Eye Res 11:187–191

    Article  PubMed  Google Scholar 

  34. Freeman G (2001) Cystoid macular oedema in uveitis: an unsolved problem. Eye 15:12–17

    PubMed  CAS  Google Scholar 

  35. Funatsu H, Yamashita H, Shimizu E, Kojima R, Hori S (2001) Relationship between vascular endothelial growth factor and interleukin-6 in diabetic retinopathy. Relationship between vascular endothelial growth factor and interleukin- 6 in diabetic retinopathy. Retina 21:469–477

    Article  PubMed  CAS  Google Scholar 

  36. Funatsu H, Yamashita H, Ikeda T, Nakanishi Y, Kitano S, Hori S (2002) Angiotensin II and vascular endothelial growth factor in the vitreous fluid of patients with diabetic macular edema and other retinal disorders. Am J Ophthalmol 133:537–543

    Article  PubMed  CAS  Google Scholar 

  37. Funatsu H, Yamashita H, Sakata K, Noma H, Mimura T, Suzuki M, Eguchi S, Hori S (2005) Vitreous levels of vascular endothelial growth factor and intercellular adhesion molecule 1 are related to diabetic macular edema. Ophthalmology 112:806–816

    Article  PubMed  Google Scholar 

  38. Gardiner TA, Gibson DS, de Gooyer TE, de la Cruz VF, McDonald DM, Stitt AW (2005) Inhibition of tumor necrosis factor-alpha improves physiological angiogenesis and reduces pathological neovascularization in ischemic retinopathy. Am J Pathol 166:637–644

    PubMed  CAS  Google Scholar 

  39. Greenberg PB, Martidis A, Rogers AH, Duker JS, Reichel E (2002) Intravitreal triamcinolone acetonide for macular oedema due to central retinal vein occlusion. Br J Ophthalmol 86:247–248

    Article  PubMed  Google Scholar 

  40. Grisanti S, Biester S, Peters S, Tatar O, Ziemssen F, Bartz-Schmidt KU, Tuebingen Bevacizumab Study Group (2006) Intracameral bevacizumab for iris rubeosis. Am J Ophthalmol 142:158–160

    Article  PubMed  CAS  Google Scholar 

  41. Grossniklaus HE, Ling JX, Wallace TM, Dithmar S, Lawson DH, Cohen C, et al. (2002) Macrophage and retinal pigment epitheliumexpression of angiogenic cytokines in choroidal neovascularization. Mol Vis 8:119–126

    PubMed  CAS  Google Scholar 

  42. Haritoglou C, Kook D, Neubauer A, Wolf A, Priglinger S, Strauss R, Gandorfer A, Ulbig M, Kampik A (2006) Intravitreal bevacizumab (Avastin) therapy for persistent diffuse diabetic macular edema. Retina 26:999–1005

    Article  PubMed  Google Scholar 

  43. Hangai M, He S, Hoffmann S, Lim JI, Ryan SJ, Hinton DR (2006) Sequential induction of angiogenic growth factors by TNF-alpha in choroidal endothelial cells. J Neuroimmunol 171:45–56

    Article  PubMed  CAS  Google Scholar 

  44. Hawrami K, Hitman GA, Rema M, Snehalatha C, Viswanathan M, Ramachandran A, Mohan V (1996) An association in non-insulin-dependent diabetes mellitus subjects between susceptibility to retinopathy and tumor necrosis factor polymorphism. Hum Immunol 46:49–54

    Article  PubMed  CAS  Google Scholar 

  45. Ishida S, YamashiroK, UsuiT, KajiY, Ogura Y, Hida T, Honda Y, Oguchi Y, Adamis AP (2003) Leukocytes mediate retinal vascular remodeling during development and vasoobliteration in disease. Nat Med 9:781–788

    Article  PubMed  CAS  Google Scholar 

  46. Ishida S, Usui T, YamashiroK, KajiY, Ahmed E, Carrasquillo KG, et al. (2003) Vegf164 is proinflammatory in the diabetic retina. Invest Ophthalmol Vis Sci 44:2155–2162

    Article  PubMed  Google Scholar 

  47. Ishida S, Usui T, Yamashiro K, Kaji Y, Amano S, Ogura Y, Hida T, Oguchi Y, Ambati J, Miller J W, Gragoudas ES, Ng YS, D'Amore PA, Shima DT, Adamis AP (2003) VEGF164-mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascularization. J Exp Med 198:483–489

    Article  PubMed  CAS  Google Scholar 

  48. Iyer VR, Eisen MB, Ross DT, Schuler G, Moore T, Lee JCF, Trent M, Staudt LM, Hudson JJ, Boguski MS, Lashkari DL, Shalon D, Botstein D, Brown PO (1999) The transcriptional program in response of human fibroblasts to serum. Science 293:83–87

    Article  Google Scholar 

  49. Jaffe GJ, Ben-Nun J, Guo H, Dunn J P, Ashton P (2000) Fluocinolone acetonide sustained drug delivery device to treat severe uveitis. Ophthalmology 107:2024–2033

    Article  PubMed  CAS  Google Scholar 

  50. Jaffe GJ, Yang CH, Guo H, Denny J P, Lima C, Ashton P (2000) Safety and pharmacokinetics of an intraocular fluocinolone acetonide sustained delivery device. Invest Ophthalmol Vis Sci 41:3569–3575

    PubMed  CAS  Google Scholar 

  51. Jonas JB, Sofker A (2001) Intraocular injection of crystalline cortisone as adjunctive treatment of diabetic macular edema. Am J Ophthalmol 132:425–427

    Article  PubMed  CAS  Google Scholar 

  52. Jonas JB, Kreissig I, Degenring RF (2002) Intravitreal triamcinolone acetonide as treatment of macular edema in central retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol 240:782–783

    Article  PubMed  Google Scholar 

  53. Jonas JB, Kreissig I, Sofker A, Degenring RF (2003) Intravitreal injection of triamcinolone for diffuse diabetic macular edema. Arch Ophthalmol 121:57–61

    Article  PubMed  CAS  Google Scholar 

  54. Jonas JB, Spandau UH, Kamppeter BA, Vossmerbaeumer U, Harder B, Sauder G (2006) Repeated intravitreal high-dosage injections of triamcinolone acetonide for diffuse diabetic macular edema. Ophthalmology 113:800–804

    Article  PubMed  Google Scholar 

  55. Joussen AM, Huang S, Poulaki V, Camphausen K, Beecken WD, Kirchhof B, Adamis AP (2001) In vivo retinal gene expression in early diabetes. Invest Ophthalmol Vis Sci 42:3047–3057

    PubMed  CAS  Google Scholar 

  56. Joussen AM, Murata T, Tsujikawa A, Kirchhof B, Bursell SE, Adamis AP (2001) Leukocyte-mediated endothelial cell injury and death in the diabetic retina. Am J Pathol 158:147–152

    PubMed  CAS  Google Scholar 

  57. Joussen AM, Poulaki V, Mitsiades N, Kirchhof B, Koizumi K, Dohmen S, Adamis AP (2002) Potential use of nonsteroidal anti-inflammatory drugs for prevention of diabetic vascular changes: Aspirin prevents diabetic leakage and leukocyte adhesion through inhibition of TNF-a. FASEB J 16:438–440

    PubMed  CAS  Google Scholar 

  58. Joussen AM, Poulaki V, Qin W, Kirchhof B, Mitsiades N, Wiegand SJ, Rudge J, Yancopoulos GD, Adamis AP (2002) Retinal vascular endothelial growth factor induces intercellular adhesionmolecule-1 and endothelial nitric oxide synthase expression and initiates early diabetic retinal leukocyte adhesion in vivo. Am J Pathol 160:501–509

    PubMed  CAS  Google Scholar 

  59. Joussen AM, Qin W, Poulaki V, Wiegand S, Yancopoulos GD, Adamis AP (2002) Endogenous VEGF induces retinal ICAM-1 and eNOS expression and initiates early diabetic retinal leukostasis. Am J Pathol 160:501–509

    PubMed  CAS  Google Scholar 

  60. Joussen AM, Poulaki V, Mitsiades N, Cai W Y, Suzuma I, Pak J, Ju ST, Rook SL, Esser P, Mitsiades CS, Kirchhof B, Adamis A P, Aiello LP (2003) Suppression of Fas-FasL-induced endothelial cell apoptosis prevents diabetic blood-retinal barrier breakdown in a model of streptozotocin-induced diabetes. FASEB J 17:76–78

    PubMed  CAS  Google Scholar 

  61. Joussen AM, Poulaki V, Le ML, Koizumi K, Esser C, Janicki H, Schraermeyer U, Kociok N, Fauser S, Kirchhof B, Kern TS, Adamis AP (2004) A central role for inflammation in the pathogenesis of diabetic retinopathy. FASEB J 18:1450–1452

    PubMed  CAS  Google Scholar 

  62. Kern TS, Engerman RL (1995) Galactose-induced retinal microangiopathy in rats. Invest Ophthalmol Vis Sci 36:490–496

    PubMed  CAS  Google Scholar 

  63. Kern TS, Engerman RL (1996) A mouse model of diabetic retinopathy. Arch Ophthalmol 114:986–990

    PubMed  CAS  Google Scholar 

  64. Khosla PK, Seth V, Tiwari HK, Saraya AK (1982) Effect of aspirin on platelet aggregation in diabetes mellitus. Diabetologia 23(2):104–117

    Article  PubMed  CAS  Google Scholar 

  65. Klein R, Klein BE, Moss SE, Cruickshanks KJ (1993) Wisconsin epidemiologic study of diabetic retinopathy. XV. The long term incidence of macular edema. Ophthalmology 102:7–16

    Google Scholar 

  66. Klein R, Klein BE, Moss SE, Cruickshanks KJ (1998) The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XVII. The 14-year incidence and progression of diabetic retinopathy and associated risk factors in type 1 diabetes. Ophthalmology 105:1801–1815

    Article  PubMed  CAS  Google Scholar 

  67. Kucia M, Jankowski K, Reca R, Wysoczynski M, Bandura L, Allendorf DJ, Zhang J, Ratajczak J, Ratajczak MZ (2004) CXCR4-SDF-1 signalling, locomotion, chemotaxis and adhesion. J Mol Histol 35:233–245

    Article  PubMed  CAS  Google Scholar 

  68. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306–1309

    Article  PubMed  CAS  Google Scholar 

  69. Lim JW, Kim H, Kim KH (2001) Nuclear factor-kappaB regulates cyclooxygenase-2 expression and cell proliferation in human gastric cancer cells. Lab Invest 81:349–360

    PubMed  CAS  Google Scholar 

  70. Limb GA, Chignell AH, Green W, LeRoy F, Dumonde DC (1996) Distribution of TNF alpha and its reactive vascular adhesion molecules in fibrovascular membranes of proliferative diabetic retinopathy. Br J Ophthalmol 80:168–173

    Article  PubMed  CAS  Google Scholar 

  71. Limb GA, Hickman-Casey J, Hollified RD, Chignell AH (1999) Vascular adhesion molecules in vitreous from eyes with proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci 40:2453–2457

    PubMed  CAS  Google Scholar 

  72. Limb GA, Webster L, Soomro H, Janikoun S, Shilling J (1999) Platelet expression of tumour necrosis factor-alpha (TNF-alpha), TNF receptors and intercellular adhesion molecule-1 (ICAM-1) in patients with proliferative diabetic retinopathy. Clin Exp Immunol 118:213–218

    Article  PubMed  CAS  Google Scholar 

  73. Martidis A, Duker JS, Greenberg PB, Rogers AH, Puliafito CA, Reichel E, Baumal C (2002) Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology 109:920–927

    Article  PubMed  Google Scholar 

  74. McCormack K (1998) Roles of COX-1 and COX-2. J Rheumatol 25:2279–2281

    PubMed  CAS  Google Scholar 

  75. McLeod DS, Lefer DJ, Merges C, Lutty GA (1995) Enhanced expression of intracellular adhesion molecule-1 and P-selectin in the diabetic human retina and choroid. Am J Pathol 147:642–653

    PubMed  CAS  Google Scholar 

  76. Meleth AD, Agron E, Chan CC, Reed GF, Arora K, Byrnes G, Csaky KG, Ferris FL 3rd, Chew EY (2005) Seruminflammatory markers in diabetic retinopathy. Invest Ophthalmol Vis Sci 46:4295–4301

    Article  PubMed  Google Scholar 

  77. Miyamoto K, Hiroshiba N, Tsujikawa A, Ogura Y (1998) In vivo demonstration of increased leukocyte entrapment in retinal microcirculation of diabetic rats. Invest Ophthalmol Vis Sci 39:2190–2194

    PubMed  CAS  Google Scholar 

  78. Miyamoto K, Khosrof S, Bursell SE, Moromizato Y, Aiello LP,Ogura Y, Adamis AP (2000) Vascular endothelial growth factor-induced retinal vascular permeability ismediated by intercellular adhesion molecule-1 (ICAM-1). Am J Pathol 156:1733–1739

    PubMed  CAS  Google Scholar 

  79. Mizutani M, Kern TS, Lorenzi M (1996) Accelerated death of retinal microvascular cells in human and experimental diabetic retinopathy. J Clin Invest 97:2883–2890

    Article  PubMed  CAS  Google Scholar 

  80. Moshfeghi DM, Kaiser PK, Scott IU, Sears JE, Benz M, Sinesterra J P, Kaiser RS, Bakri SJ, Maturi RK, Belmont J, Beer PM, Murray TG, Quiroz-Mercado H, Meiler WF (2003) Acute endophthalmitis following intravitreal triamcinolone acetonide injection. Am J Ophthalmol 136:793–796

    Google Scholar 

  81. Nagata S, Golstein P (1995) The Fas death factor. Science 267:1449–1456

    Article  PubMed  CAS  Google Scholar 

  82. Ng E W, Adamis AP (2005) Targeting angiogenesis, the underlying disorder in neovascular age-related macular degeneration. Can J Ophthalmol 40:352–368

    PubMed  Google Scholar 

  83. Nguyen QD, Tatlipinar S, Shah SM, Haller JA, Quinlan E, Sung J, Zimmer-Galler I, Do D V, Campochiaro PA (2006) Vascular endothelial growth factor is a critical stimulus for diabetic macular edema. Am J Ophthalmol 142(6): 961–969

    Article  PubMed  CAS  Google Scholar 

  84. Nishihira J (1998) Novel pathophysiological aspects of macrophage migration inhibitory factor (review). Int J Mol Med 2:17–28

    PubMed  CAS  Google Scholar 

  85. Oh H, Takagi H, Takagi C, Suzuma K, Otani A, Ishida K, Matsumura M, Ogura Y, Honda Y (1999) The potential angiogenic role of macrophages in the formation of choroidal neovascular membranes. Invest Ophthalmol Vis Sci 40:1891–1898

    PubMed  CAS  Google Scholar 

  86. Pairet M, Engelhardt G (1996) Distinct isoforms (COX-1 and COX-2) of cyclooxygenase: possible physiological and therapeutic implications. Fundam Clin Pharmacol 10:1–17

    Article  PubMed  CAS  Google Scholar 

  87. Pillinger MH, Capodici C, Rosenthal P, Kheterpal N, Hanft S, Philips MR, Weissmann G (1998) Modes of action of aspirin-like drugs: salycylates inhibit erk activation and integrin-dependent neutrophil adhesion. Proc Natl Acad Sci USA 95:14540–14545

    Article  PubMed  CAS  Google Scholar 

  88. Powell EDU, Field RA (1964) Diabetic retinopathy in rheumatoid arthritis. Lancet 2:17–18

    Article  PubMed  CAS  Google Scholar 

  89. Qaum T, Xu Q, Joussen AM, Clemens MW, Qin W, Miyamoto K, Hassessian H, Wiegand SJ, Rudge J, Yancopoulos GD, Adamis AP (2001) VEGF-initiated blood-retinal barrier breakdown in early diabetes. Invest Ophthalmol Vis Sci 42:2408–2413

    PubMed  CAS  Google Scholar 

  90. Roberts WG, Palade GE (1995) Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J Cell Sci 108:2369–2379

    PubMed  CAS  Google Scholar 

  91. Rojas B, Zafirakis P, Christen W, Markomichelakis NN, Foster CS (1999) Medical treatment of macular edema in patients with uveitis. Doc Ophthalmol 97:399–407

    Article  PubMed  CAS  Google Scholar 

  92. Romero IA, Radewicz K, Jubin E, Michel CC, Greenwood J, Couraud PO, Adamson P (2003) Changes in cytoskeletal and tight junctional proteins correlate with decreased permeability induced by dexamethasone in cultured rat brain endothelial cells. Neurosci Lett 334:112–116

    Article  Google Scholar 

  93. Roth DB, Chieh J, Spirn MJ, Green SN, Yarian DL, Chaudhry NA (2003) Noninfectious endophthalmitis associated with intravitreal triamcinolone injection. Arch Ophthalmol 121:1279–1282

    Article  PubMed  Google Scholar 

  94. Safieh-Garabedian B, Dardenne M, Kanaan SA, Atweh SF, Jabbur SJ, Saade NE (2000) The role of cytokines and prostaglandin-E(2) in thymulin induced hyperalgesia. Neuropharmacology 39:1653–1661

    Article  PubMed  CAS  Google Scholar 

  95. Sakane S, Nishihira J, Hirokawa J, Yoshimura H, Honda T, Aoki K, Tagami S, Kawakami Y (1999) Regulation of macrophage migration inhibitory factor (MIF) expression by glucose and insulin in adipocytes in vitro. Mol Med 5:361–371

    Google Scholar 

  96. Sakurai E, Anand A, Ambati BK, van Rooijen N, Ambati J (2003) Macrophage depletion inhibits experimental choroidal neovascularization. Invest Ophthalmol Vis Sci 44:3578–3585

    Article  PubMed  Google Scholar 

  97. Sfikakis P P, Markomichelakis N, Theodossiadis G P, Grigoropoulos V, Katsilambros N, Theodossiadis PG (2005) Regression of sight-threatening macular edema in type 2 diabetes following treatment with the anti-tumor necrosis factor monoclonal antibody infliximab. Diabetes Care 28:445–447

    Article  PubMed  Google Scholar 

  98. Silva Paula J, Jorge R, Alves Costa R, Rodrigues Mde L, Scott IU (2006) Short-term results of intravitreal bevacizumab (Avastin) on anterior segment neovascularization in neovascular glaucoma. Acta Ophthalmol Scand 84:556–557

    Article  PubMed  Google Scholar 

  99. Southern E, Mir K, Schepinov M (1999) Molecular interactions on microarrays. Nat Genet 21:S5–S9

    Article  Google Scholar 

  100. Spaide RF, Fisher YL (2006) Intravitreal bevacizumab (Avastin) treatment of proliferative diabetic retinopathy complicated by vitreous hemorrhage. Retina 26:275–278

    Article  PubMed  Google Scholar 

  101. Spranger J, Meyer-Schwickerath R, Klein M, Schatz H, Pfeiffer A (1995) TNF-alpha Konzentration in Glaskörper. Anstieg bei neovaskulären Erkrankungen und proliferativer diabetischer Retinopathie. Med Klin 90:134–137

    CAS  Google Scholar 

  102. Thach AB, Dugel PU, Flindall RJ, Sipperley JO, Sneed SR (1997) A comparison of retrobulbar versus subtenon's corticosteroid therapy for cystoid macular edema refractory to topical medications. Ophthalmology 104:2003–2008

    PubMed  CAS  Google Scholar 

  103. Tolentino MJ, Miller J W, Gragoudas ES, Jakobiec FA, Flynn E, Chatzistefanou K, Ferrara N, Adamis AP (1996) Intravitreous injections of vascular endothelial growth factor produce retinal ischemia and microangiopathy in an adult primate. Ophthalmology 103:1820–1828

    PubMed  CAS  Google Scholar 

  104. Tsutsumi C, Sonoda KH, Egashira K, Qiao H, Hisatomi T, Nakao S, Ishibashi M, Charo IF, Sakamoto T, Murata T, Ishibashi T (2003) The critical role of ocular-infiltrating macrophages in the development of choroidal neovascularization. J Leukoc Biol 74:25–32

    Article  PubMed  CAS  Google Scholar 

  105. Usui T, Ishida S, YamashiroK, Kaji Y, Poulaki V, Moore J, et al. (2004) Vegf 164(165) as the pathological isoform: Differential leukocyte and endothelial responses through vegfr1 and vegfr2. Invest Ophthalmol Vis Sci 45: 368–374

    Article  PubMed  Google Scholar 

  106. Wallach D (1997) Cell death induction by TNF: a matter of self control. Trends Biochem Sci 22:107–109

    Article  PubMed  CAS  Google Scholar 

  107. Watanabe D, Suzuma K, Suzuma I, Ohashi H, Ojima T, Kurimoto M, Murakami T, Kimura T, Takagi H (2005) Vitreous levels of angiopoietin 2 and vascular endothelial growth factor in patients with proliferative diabetic retinopathy. Am J Ophthalmol 139:476–481

    Article  PubMed  CAS  Google Scholar 

  108. Watanabe D, Suzuma K, Matsui S, Kurimoto M, Kiryu J, Kita M, Suzuma I, Ohashi H, Ojima T, Murakami T, Kobayashi T, Masuda S, Nagao M, Yoshimura N, Takagi H (2005) Erythropoietin as a retinal angiogenic factor in proliferative diabetic retinopathy. N Engl J Med 353: 782–792

    Article  PubMed  CAS  Google Scholar 

  109. Weissmann G (1991) Aspirin. Sci Am 264:84–96

    Article  PubMed  CAS  Google Scholar 

  110. Wingate RJ, Beaumont PE (1999) Intravitreal triamcinolone and elevated intraocular pressure. Aust NZ J Ophthalmol 27:431–432

    Article  CAS  Google Scholar 

  111. Yoshikawa K, Kotake S, Ichiishi A, Sasamoto Y, Kosaka S, Matsuda J (1995) Posterior sub-tenon injections of repository corticosteroids in uveitis patients with cystoidmacular edema. Jpn J Ophthalmol 39:71–76

    PubMed  CAS  Google Scholar 

  112. Young S, Larkin G, Branley M, Lightman S (2001) Safety and efficacy of intravitreal triamcinolone for cystoid macular oedema in uveitis. Clin Exp Ophthalmol 29:2–6

    Article  CAS  Google Scholar 

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  1. Department of Ophthalmology, University of Duesseldorf, Moorenstrabe 5, Duesseldorf, 40225, Germany

    Antonia M Joussen

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  1. Antonia M Joussen
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Joussen, A. (2009). Is Diabetic Retinopathy an Inflammatory Disease? Inflammation as a Stimulus for Vascular Leakage and Proliferati on. In: Uveitis and Immunological Disorders. Essentials in Ophthalmology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-69459-5_4

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  • DOI: https://doi.org/10.1007/978-3-540-69459-5_4

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