Angiogenesis and Inflammation Crosstalk in Diabetic Retinopathy

Journal of Cellular Biochemistry

Volumn , Issue , 2016, Pages 2443-2453

  Capitão, Margarida ^a   Soares, Raquel ^a,b  

^a University of Porto   (Portugal)

^b UNIVERSITY OF PORTO   (Portugal)

Author keywords

DIABETIC MACULAR EDEMA; ENDOTHELIAL PROGENITOR CELLS; NEOVASCULARIZATION; THERAPEUTIC STRATEGIES; VEGF

Indexed keywords

ADVANCED GLYCATION END PRODUCT; ANGIOPOIETIN 2; CYCLOOXYGENASE 2; ENDOTHELIAL NITRIC OXIDE SYNTHASE; GELATINASE A; GELATINASE B; GROWTH FACTOR; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 12; INTERLEUKIN 1BETA; INTERLEUKIN 6; INTERLEUKIN 8; MONOCYTE CHEMOTACTIC PROTEIN 1; NITRIC OXIDE SYNTHASE; PATHOGEN ASSOCIATED MOLECULAR PATTERN; PIGMENT EPITHELIUM DERIVED FACTOR; POLYOL; PROTEIN KINASE C; STROMAL CELL DERIVED FACTOR 1; TUMOR NECROSIS FACTOR; VASCULAR CELL ADHESION MOLECULE 1; VASCULOTROPIN;

ANGIOGENESIS; ARTICLE; BLOOD VESSEL PERMEABILITY; CLINICAL CLASSIFICATION; DIABETIC MACULAR EDEMA; DIABETIC PATIENT; DIABETIC RETINOPATHY; DISEASE COURSE; DYSTROPHY; ENDOTHELIAL PROGENITOR CELL; ENZYME ACTIVATION; HUMAN; HYPERGLYCEMIA; HYPOXEMIA; INFLAMMATION; LASER COAGULATION; LEUKOSTASIS; METABOLIC REGULATION; MORBIDITY; NERVE DEGENERATION; OXIDATIVE STRESS; PERICYTE; PRIORITY JOURNAL; PROLIFERATIVE DIABETIC RETINOPATHY; REMISSION; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; RESPIRATORY BURST; RETINA CAPILLARY; RETINA NEOVASCULARIZATION; STEROID THERAPY; VISUAL ACUITY; VISUAL IMPAIRMENT; VITREOUS HEMORRHAGE;

EID: 84986183472     PISSN: 07302312     EISSN: 10974644     Source Type: Journal    
DOI: 10.1002/jcb.25575     Document Type: Article

References (159)

1. Adamiec-Mroczek J, Zajac-Pytrus H, Misiuk-Hojlo M. 2015. Caspase-dependent apoptosis of retinal ganglion cells during the development of diabetic retinopathy. Adv Clin Exp Med 24(3):531–535.
2. Adamis AP. 2002. Is diabetic retinopathy an inflammatory disease? Br J Ophthalmol 86(4):363–365.
3. Agrawal NK, Kant S. 2014. Targeting inflammation in diabetes: Newer therapeutic options. World J Diabetes 5(5):697–710.
4. Aiello LP, Nguyen H, Aiello L, 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(22):1480–1487.
5. Alder VA, Su EN, Yu D, Cringle S, Yu P. 1997. Diabetic retinopathy: Early functional changes. Clin Exp Pharmacol Physiol 24(9–10):785–788.
6. Arumi JG, Boixadera A, Martinez-Castillo V, Corocostequi B. 2009. Transconjunctival sutureless 23-gauge vitrectomy for diabetic retinopathy. Review. Curr Diabetes Rev 5(1):63–66.
7. Asahara T, Kawamoto A, Masuda H. 2011. Concise review: Circulating endothelial progenitor cells for vascular medicine. Stem Cells 29(11):1650–1655.
8. Ashton N, Ward B, Serpell G. 1954. Effect of oxygen on developing retinal vessels with particular reference to the problem of retrolental fibroplasia. Br J Ophthalmol 38(7):397–432.
9. Avogaro A, Albiero M, Menegazzo L, de Kreuzenberg S, Fadini GP. 2011. Endothelial dysfunction in diabetes: The role of reparatory mechanisms. Diabetes Care 34(Suppl 2):S285–290.
10. Ayalasomayajula SP, Kompella UB. 2003. Celecoxib, a selective cyclooxygenase-2 inhibitor, inhibits retinal vascular endothelial growth factor expression and vascular leakage in a streptozotocin-induced diabetic rat model. Eur J Pharmacol 458(3):283–289.
11. Barile GR, Pachydaki S, Tari S, Lee SR, Donmoyer C, Ma W, Rong L, Buciarelli L, Wendt T, Hörig H, Hudson B, Qu W, Weinberg A, Yan S, Schmidt A. 2005. The RAGE axis in early diabetic retinopathy. Invest Ophthalmol Vis Sci 46(8):2916–2924.
12. Barot M, Gokulghandi M, Patel S, Mitra A. 2013. Microvascular complications and diabetic retinopathy: Recent advances and future implications. Future Med Chem 5(3):301–314.
13. Basavarajappa HD, Crofford L, Wilder R, Hla T. 2014. Synthesis and mechanistic studies of a novel homoisoflavanone inhibitor of endothelial cell growth. PLoS One 9(4):e95694.
14. Ben-Av P, Crofford L, Wilder R, Hla T. 1995. Induction of vascular endothelial growth factor expression in synovial fibroblasts by prostaglandin E and interleukin-1: A potential mechanism for inflammatory angiogenesis. FEBS Lett 372(1):83–87.
15. Bhagat N, Grigorian R, Tutela A, Zarbin M. 2009. Diabetic macular edema: Pathogenesis and treatment. Surv Ophthalmol 54(1):1–32.
16. Bola C, Bartlett H, Eperjesi F. 2014. Resveratrol and the eye: Activity and molecular mechanisms. Graefes Arch Clin Exp Ophthalmol 252(5):699–713.
17. Boscia F. 2010. Current approaches to the management of diabetic retinopathy and diabetic macular oedema. Drugs 70(16):2171–2200.
18. Boyer DS, Hopkins J, Sorof J, Ehrlich J. 2013. Anti-vascular endothelial growth factor therapy for diabetic macular edema. Ther Adv Endocrinol Metab 4(6):151–169.
19. Brown JB, Pedula KL, Summers KH. 2003. Diabetic retinopathy: Contemporary prevalence in a well-controlled population. Diabetes Care 26(9):2637–2642.
20. Brucklacher RM, Patel K, van Guilder HD, Bixler G, Barber A, Antonetti DA, Lin C, Lanoue K, Gardner T, Bronson S, Freeman W. 2008. Whole genome assessment of the retinal response to diabetes reveals a progressive neurovascular inflammatory response. BMC Med Genomics 1:26.
21. Bursell SE, Takagi C, Clermont A, Takagi H, Mori F, Ishii H, King G. 1997. Specific retinal diacylglycerol and protein kinase C beta isoform modulation mimics abnormal retinal hemodynamics in diabetic rats. Invest Ophthalmol Vis Sci 38(13):2711–2720.
22. Busik JV, Mohr S, Grant MB. 2008. Hyperglycemia-induced reactive oxygen species toxicity to endothelial cells is dependent on paracrine mediators. Diabetes 57(7):1952–1965.
23. Cade WT. 2008. Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Phys Ther 88(11):1322–1335.
24. Cai J, Boulton M. 2002. The pathogenesis of diabetic retinopathy: Old concepts and new questions. Eye (Lond) 16(3):242–260.
25. Cancarini A, Costagliola A, Dell'omoo R, Romano M, Morescalchi F, Agnifili L, Ruggeri G, Semeraro F. 2014. Effect of intravitreal bevacizumab on serum, aqueous, and vitreous humor levels of erythropoietin in patients with proliferative diabetic retinopathy. Minerva Endocrinol 39(4):305–311.
26. Capeans C, De Rojas M, Lojo S, Salorio M. 1998. C-C chemokines in the vitreous of patients with proliferative vitreoretinopathy and proliferative diabetic retinopathy. Retina 18(6):546–550.
27. Carmeliet P, Jain RK. 2011. Molecular mechanisms and clinical applications of angiogenesis. Nature 473(7347):298–307.
28. Cheng T, Cao W, Wen R, Steinberg RH, LaVail M. 1998. Prostaglandin E2 induces vascular endothelial growth factor and basic fibroblast growth factor mRNA expression in cultured rat Muller cells. Invest Ophthalmol Vis Sci 39(3):581–591.
29. Chibber R, Molinatti PA, Kohner EM. 1999. Intracellular protein glycation in cultured retinal capillary pericytes and endothelial cells exposed to high-glucose concentration. Cell Mol Biol (Noisy-le-grand) 45(1):47–57.
30. Ciulla TA, Amador AG, Zinman B. 2003. Diabetic retinopathy and diabetic macular edema: Pathophysiology, screening, and novel therapies. Diabetes Care 26(9):2653–2664.
31. Correia JA, Almeida J, Anselmo J, Ayala M, Cardoso SM, Costa A, Dores J, Duarte JS, Duarte R, Ferreira H, Medina JL, Nunes JS, Pereira M, Raposo J Diabetes: Factos e Números—O Ano de 2014—Relatório Anual do Observatório Nacional da Diabetes 11/2015. 64.
32. Costagliola C, Romano V, De Tollis M, Aceto F, dell'Omo R. 2013. TNF-alpha levels in tears: A novel biomarker to assess the degree of diabetic retinopathy. Mediators Inflamm 2013:629529.
33. Costagliola C, Daniele A, dell'Omo R, Romano MR, Aceto F, Agnifili L, Semeraro F, Porcellini A. 2013. Aqueous humor levels of vascular endothelial growth factor and adiponectin in patients with type 2 diabetes before and after intravitreal bevacizumab injection. Exp Eye Res 110:50–54.
34. Costagliola C. 1990. Oxidative state of glutathione in red blood cells and plasma of diabetic patients: In vivo and in vitro study. Clin Physiol Biochem 8(4):204–210.
35. Cunha-Vaz JG. 1976. The blood-retinal barriers. Doc Ophthalmol 41(2):287–327.
36. Demircan N, Safran BG, Soylu M, Ozcan AA, Sizmaz S. 2006. Determination of vitreous interleukin-1 (IL-1) and tumour necrosis factor (TNF) levels in proliferative diabetic retinopathy. Eye (Lond) 20(12):1366–1369.
37. dell'Omo R, Semeraro F, Bamonte G, Cifariello F, Romano MR, Costagliola C. 2013. Vitreous mediators in retinal hyoxic diseases. Mediators Inflamm 2013:935301.
38. Derevjanik NL, Vinores SA, Xiao WH, Mori K, Turon T, Hudish T, Dong S, Campochiaro PA. 2002. Quantitative assessment of the integrity of the blood-retinal barrier in mice. Invest Ophthalmol Vis Sci 43(7):2462–2467.
39. Doganay S, Evereklioglu C, Er H, Turkoz Y, Sevinc A, Mehmet N, Savli H. 2002. Comparison of serum NO, TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 levels with grades of retinopathy in patients with diabetes mellitus. Eye (Lond) 16(2):163–170.
40. Domingueti CP, Dusse L, Carvalho M, de Sousa L, Gomes K, Fernandes A. 2016. Diabetes mellitus: The linkage between oxidative stress, inflammation, hypercoagulability and vascular complications. J Diabetes Complications 30(4):7738–7745.
41. Dor Y, Porat R, Keshet E. 2001. Vascular endothelial growth factor and vascular adjustments to perturbations in oxygen homeostasis. Am J Physiol Cell Physiol 280(6):C1367–1374.
42. Du Y, Sarthy VP, Kern TS. 2004. Interaction between NO and COX pathways in retinal cells exposed to elevated glucose and retina of diabetic rats. Am J Physiol Regul Integr Comp Physiol 287(4):735–741.
43. Egan CG, Lavery R, Caporali F, Fondelli C, Laghi-Pasini F, Dotta F, Sorrentino V. 2008. Generalised reduction of putative endothelial progenitors and CXCR4-positive peripheral blood cells in type 2 diabetes. Diabetologia 51(7):1296–1305.
44. El-Asrar AM. 2012. Role of inflammation in the pathogenesis of diabetic retinopathy. Middle East Afr J Ophthalmol 19(1):70–74.
45. Ellis TP, Choudhury RH, Kaul K, Chopra M, Kohner EM, Tar JM, Chibber R. 2013. Diabetic retinopathy and atherosclerosis: Is there a link? Curr Diabetes Rev 9(2):146–160.
46. Fadini GP, Avogaro A. 2013. Diabetes impairs mobilization of stem cells for the treatment of cardiovascular disease: A meta-regression analysis. Int J Cardiol 168(2):892–897.
47. Fadini GP, Sartore S, Schiavon M, Albiero M, Baesso I, Cabrelle A, Agostini C, Avogaro A. 2006. Diabetes impairs progenitor cell mobilisation after hindlimb ischaemia-reperfusion injury in rats. Diabetologia 49(12):3075–3084.
48. Falavarjani KG, Nguyen QD. 2013. Adverse events and complications associated with intravitreal injection of anti-VEGF agents: A review of literature. Eye (Lond) 27(7):787–794.
49. Feener EP. 2010. Plasma kallikrein and diabetic macular edema. Curr Diab Rep 10(4):270–275.
50. Ferris F. 1996. Early photocoagulation in patients with either type I or type II diabetes. Trans Am Ophthalmol Soc 94:505–537.
51. Folkman J, Ingber D. 1992. Inhibition of angiogenesis. Semin Cancer Biol 3(2):89–96.
52. Fong DS, Aiello L, Ferris F, Klein R. 2004. Diabetic retinopathy. Diabetes Care 27(10):2540–2553.
53. Funatsu H, Yamashita H, Ikeda T, Mimura T, Eguchi S, Hori S. 2002. Increased levels of vascular endothelial growth factor and interleukin-6 in the aqueous humor of diabetics with macular edema. Am J Ophthalmol 133(1):70–77.
54. Funatsu H, Yamashita H, Ikeda T, Mimura T, Eguchi S, Hori S. 2003. Vitreous levels of interleukin-6 and vascular endothelial growth factor are related to diabetic macular edema. Ophthalmology 110(9):1690–1696.
55. Funk M, Schmidinger G, Maar N, Bolz M, Benesch T, Zlabinger GJ, Schmidt-Erfurth UM. 2010. Angiogenic and inflammatory markers in the intraocular fluid of eyes with diabetic macular edema and influence of therapy with bevacizumab. Retina 30(9):1412–1419.
56. Gallagher KA, Liu ZJ, Xiao M, Chen H, Goldstein LJ, Buerk DG, Nedeau A, Thom SR. 2007. Diabetic impairments in NO-mediated endothelial progenitor cell mobilization and homing are reversed by hyperoxia and SDF-1 alpha. J Clin Invest 117(5):1249–1259.
57. Giebel SJ, Menicucci G, McGuire PG, Das A. 2005. Matrix metalloproteinases in early diabetic retinopathy and their role in alteration of the blood-retinal barrier. Lab Invest 85(5):597–597
58. Goldberg RB. 2009. Cytokine and cytokine-like inflammation markers, endothelial dysfunction, and imbalanced coagulation in development of diabetes and its complications. J Clin Endocrinol Metab 94(9):3171–3182.
59. Goldin A, Beckman JA, Schmidt AM, Creager MA. 2006. Advanced glycation end products: Sparking the development of diabetic vascular injury. Circulation 114(6):597–605.
60. Gologorsky D, Thanos A, Vavvas D. 2012. Therapeutic interventions against inflammatory and angiogenic mediators in proliferative diabetic retinopathy. Mediators Inflamm 2012:629452.
61. Grigsby JG, Cardona SM, Pouw C, Muniz A, Mendiola AS, Tsin AT, Allen DM, Cardona AE. 2014. The role of microglia in diabetic retinopathy. J Ophthalmol 2014:705–783.
62. Grzybowski A, Ascaso FJ. 2015. The evolution of laser therapy in ophthalmology: A perspective on the interactions between photons, patients, physicians, and physicists: The LXX Edward Jackson Memorial Lecture. Am J Ophthalmol 159(1):206.
63. Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. 2014. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 103(2):137–149.
64. Gurler B, Vural H, Yilmaz N, Oguz H, Satici A, Aksoy N. 2000. The role of oxidative stress in diabetic retinopathy. Eye (Lond) 14(5):730–735.
65. Harris M, Flegal K, Cowie C, Eberhardt M, Goldstein DE, Little RR, Wiedmeyer HM, Byrd-Holt DD. 1998. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988-1994. Diabetes Care 21(4):518–524.
66. Heier J, Bressler N, Avery R, Bakri S, Boyer D, Brown D, Dugel P, Freund K, Glassman AR, Kim, JE, Martin DF, Pollack J, Regillo CD, Rosenfeld PJ, Schachat AP, Wells J, 3rd. 2016. Comparison of aflibercept, bevacizumab, and ranibizumab for treatment of diabetic macular edema: Extrapolation of data to clinical practice. JAMA Ophthalmol 134(1):95–99.
67. Henriques J, Vaz-Pereira S, Nascimento J, Rosa PC. 2015. Diabetic eye disease. Acta Med Port 28(1):107–113.
68. Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T. 2003. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 348(7):593–600.
69. Iandiev I, Pannicke T, Reichel M, Wiedemann P, Reichenbach A, Bringmann A. 2005. Expression of aquaporin-1 immunoreactivity by photoreceptor cells in the mouse retina. Neurosci Lett 388(2):96–99.
70. 6.th IDF Diabetes Atlas—Update. IDF, 2014.
71. Ishida S, Usui T, Yamashiro K, Kaji Y, Ahmed E, Carrasquillo KG, Amano S, Hida T, Oguchi Y, Adamis A. 2003a. VEGF164 is proinflammatory in the diabetic retina. Invest Ophthalmol Vis Sci 44(5):2155–2162.
72. Ishida S, Usui T, Yamashiro K, Kaji Y, Amano S, Ogura Y, Hida T, Oguchi Y, Ambati J, Miller JW, Gragoudas ES, Ng YS, D'Amore PA, Shima DT, Adamis A. 2003b. VEGF164-mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascularization. J Exp Med 198(3):483–489.
73. Jin M, Kashiwagi K, Iizuka Y, Tanaka Y, Imai M, Tsukahara S. 2001. Matrix metalloproteinases in human diabetic and nondiabetic vitreous. Retina 21(1):28–33.
74. João Figueira JN, José Henriques, Luis Gonçalves, Paulo Rosa, Rufino Silva, RETINOPATIA DIABÉTICA—guidelines. RD-gdl 0010 GER Portugal versão 1.0, 2009.
75. Joussen A, Poulaki V, Mitsiades N, Kirchhof B, Koizumi K, Dohmen S, Adamis A. 2002. Nonsteroidal anti-inflammatory drugs prevent early diabetic retinopathy via TNF-alpha suppression. Faseb j 16(3):438–440.
76. Kastelan S, Tomic M, Salopek-Rabatic J, Pavan J, Lukenda A, Gotovac M, Zunec R. 2013a. The association between the HLA system and retinopathy development in patients with type 1 diabetes mellitus. Coll Antropol 37(Suppl 1):65–70.
77. Kastelan S, Tomic M, Gverovic Antunica A, Salopek Rabatic J, Ljubic S. 2013b. Inflammation and pharmacological treatment in diabetic retinopathy. Mediators Inflamm 2013:213130.
78. Kern TS. 2007. Contributions of inflammatory processes to the development of the early stages of diabetic retinopathy. Exp Diabetes Res 2007:95103.
79. Khokha R, Murthy A, Weiss A. 2013. Metalloproteinases and their natural inhibitors in inflammation and immunity. Nat Rev Immunol 13(9):649–665.
80. King H, Aubert RE, Herman WH. 1998. Global burden of diabetes, 1995-2025: Prevalence, numerical estimates, and projections. Diabetes Care 21(9):1414–1431.
81. Klein R. 1995. Hyperglycemia and microvascular and macrovascular disease in diabetes. Diabetes Care 18(2):258–268.
82. Kowluru RA, Chan PS. 2007. Oxidative stress and diabetic retinopathy. Exp Diabetes Res 2007:43603.
83. Kowluru RA, Odenbach S. 2004. Role of interleukin-1beta in the development of retinopathy in rats: Effect of antioxidants. Invest Ophthalmol Vis Sci 45(11):4161–4166.
84. Kowluru RA, Zhong Q, Kanwar M. 2010. Metabolic memory and diabetic retinopathy: Role of inflammatory mediators in retinal pericytes. Exp Eye Res 90(5):617–623.
85. Koya D, King GL. 1998. Protein kinase C activation and the development of diabetic complications. Diabetes 47(6):859–866.
86. Leali D, Dell'Era P, Stabile H, Sennino B, Chambers AF, Naldini A, Sozzani S, Nico B, Ribatti D, Presta M. 2003. Osteopontin (Eta-1) and fibroblast growth factor-2 cross-talk in angiogenesis. J Immunol 171(2):1085–1093.
87. Li G, Veenstra A, Talahalli R, Wang X, Gubitosi-Klug RA, Sheibani N, Kern T. 2012. Marrow-derived cells regulate the development of early diabetic retinopathy and tactile allodynia in mice. Diabetes 61(12):3294–3303.
88. Limb GA, Chignell AH, Green W, LeRoy F, Dumonde D. 1996. Distribution of TNF alpha and its reactive vascular adhesion molecules in fibrovascular membranes of proliferative diabetic retinopathy. Br J Ophthalmol 80(2):168–173.
89. Ling R, Ramsewak V, Taylor D, Jacob J. 2002. Longitudinal study of a cohort of people with diabetes screened by the Exeter Diabetic Retinopathy Screening Programme. Eye (Lond) 16(2):140–145.
90. Loomans CJ, de Koning E, Staal F, Rookmaaker M, Verseyden C, de Boer H, Verhaar M, Braam B, Rabelink TJ, van Zonneveld A. 2004. Endothelial progenitor cell dysfunction: A novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes 53(1):195–199.
91. Lutty GA. 2013. Effects of diabetes on the eye. Invest Ophthalmol Vis Sci 54(14):Orsf81–87.
92. Maier R, Weger M, Haller-Schober E, El-Shabrawi Y, Wedrich A, Theisl A, Aigner R, Barth A, Haas A. 2008. Multiplex bead analysis of vitreous and serum concentrations of inflammatory and proangiogenic factors in diabetic patients. Mol Vis 14:637–637.
93. Mason JO, 3rd, Colagross CT, Vail R. 2006. Diabetic vitrectomy: Risks, prognosis, future trends. Curr Opin Ophthalmol 17(3):281–285.
94. McLeod D, Lefer D, Merges C, Lutty G. 1995. Enhanced expression of intracellular adhesion molecule-1 and P-selectin in the diabetic human retina and choroid. Am J Pathol 147(3):642–53.
95. Meleth A, Agron E, Chan C, Reed G, Arora K, Byrnes G, Csaky K, Ferris F, 3rd, Chew E. 2005. Serum inflammatory markers in diabetic retinopathy. Invest Ophthalmol Vis Sci 46(11):4295–4301.
96. Mitchell P, Bandello F, Schmidt-Erfurth U, Lang G, Massin P, Schlingemann R, Sutter F, Simader C, Burian G, Gerstner O, Weichselberger A. 2011. The RESTORE study: Ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology 118(4):615–625.
97. Mocan MC, Kadayifcilar S, Eldem B. 2006. Elevated intravitreal interleukin-6 levels in patients with proliferative diabetic retinopathy. Can J Ophthalmol 41(6):747–752.
98. Mohamed Q, Gillies MC, Wong TY. 2007. Management of diabetic retinopathy: A systematic review. Jama 298(8):902–916.
99. Murugeswari P, Shukla D, Rajendran A, Kim R, Namperumalsamy P, Muthukkaruppan V. 2008. Proinflammatory cytokines and angiogenic and anti-angiogenic factors in vitreous of patients with proliferative diabetic retinopathy and eales' disease. Retina 28(6):817–824.
100. Naldini A, Leali D, Pucci A, Morena E, Carraro F, Nico B, Ribatti D, Presta M. 2006. Cutting edge: IL-1beta mediates the proangiogenic activity of osteopontin-activated human monocytes. J Immunol 177(7):4267–4270.
101. Neubauer AS, Ulbig MW. 2007. Laser treatment in diabetic retinopathy. Ophthalmologica 221(2):95–102.
102. Newman DK. 2010. Surgical management of the late complications of proliferative diabetic retinopathy. Eye (Lond) 24(3):441–449.
103. Nguyen Q, Shah S, Van Anden E, Sung J, Vitale S, Campochiaro P. 2004. Supplemental oxygen improves diabetic macular edema: A pilot study. Invest Ophthalmol Vis Sci 45(2):617–624.
104. Noda K, Nakao S, Ishida S, Ishibashi T. 2012. Leukocyte adhesion molecules in diabetic retinopathy. J Ophthalmol 2012:279037.
105. Omri S, Behar-Cohen F, de Kozak Y, Sennlaub F, Verissimo L, Jonet L, Savoldelli M, Omri B, Crisanti P. 2011. Microglia/macrophages migrate through retinal epithelium barrier by a transcellular route in diabetic retinopathy: Role of PKCzeta in the Goto Kakizaki rat model. Am J Pathol 179(2):942–953.
106. Ortiz G, Salica J, Chuluyan E, Gallo J. 2014. Diabetic retinopathy: Could the alpha-1 antitrypsin be a therapeutic option? Biol Res 47:58.
107. Ozaki H, Hayashi H, Vinores S, Moromizato Y, Campochiaro P, Oshima K. 1997. Intravitreal sustained release of VEGF causes retinal neovascularization in rabbits and breakdown of the blood-retinal barrier in rabbits and primates. Exp Eye Res 64(4):505–505.
108. P, R.-E. 2013. Eye. Current Medical Diagnosis and Treatment, 2003. 42nd ed: 146–177.
109. Park YG, Roh YJ. 2016. New diagnostic and therapeutic approaches for preventing the progression of diabetic retinopathy. J Diabetes Res 2016:1753584.
110. Parks WC, Wilson CL, Lopez-Boado YS. 2004. Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev Immunol 4(8):617–629.
111. Patel J, Hykin P, Gregor Z, Boulton M, Cree I. 2005. Angiopoietin concentrations in diabetic retinopathy. Br J Ophthalmol 89(4):480–483.
112. Patel N. 2009. Targeting leukostasis for the treatment of early diabetic retinopathy. Cardiovasc Hematol Disord Drug Targets 9(3):222–229.
113. Perez VL, Caspi RR. 2015. Immune mechanisms in inflammatory and degenerative eye disease. Trends Immunol 36(6):354–363.
114. Pierce E, Avery R, Foley E, Aiello L, Smith L. 1995. Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization. Proc Natl Acad Sci USA 92(3):905–909.
115. Qazi Y, Maddula S, Ambati BK. 2009. Mediators of ocular angiogenesis. J Genet 88(4):495–515.
116. Rangasamy S, Srinivasan R, Maestas J, McGuire P, Das A. 2011. A potential role for angiopoietin 2 in the regulation of the blood-retinal barrier in diabetic retinopathy. Invest Ophthalmol Vis Sci 52(6):3784–3791.
117. Rangasamy S, McGuire PG, Das A. 2012. Diabetic retinopathy and inflammation: Novel therapeutic targets. Middle East Afr J Ophthalmol 19(1):52–59.
118. Rangasamy S, McGuire P, Franco Nitta C, Monickaraj F, Oruganti S, Das A. 2014. Chemokine mediated monocyte trafficking into the retina: Role of inflammation in alteration of the blood-retinal barrier in diabetic retinopathy. PLoS ONE 9(10):e108508.
119. Romeo G, Liu W, Asnaghi V, Kern T, Lorenzi M. 2002. Activation of nuclear factor-kappaB induced by diabetes and high glucose regulates a proapoptotic program in retinal pericytes. Diabetes 51(7):2241–2248.
120. Sakurai E, Taguchi H, Anand A, Ambati B, Gragoudas E, Miller J, Adamis A, Ambati J. 2003. Targeted disruption of the CD18 or ICAM-1 gene inhibits choroidal neovascularization. Invest Ophthalmol Vis Sci 44(6):2743–2749.
121. Sasongko MB, Wong T, Jenkins A, Nguyen T, Shaw J, Wang J. 2015. Circulating markers of inflammation and endothelial function, and their relationship to diabetic retinopathy. Diabet Med 32(5):686–691.
122. Schmidt A, Yan S, Wautier J, Stern D. 1999. Activation of receptor for advanced glycation end products: A mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis. Circ Res 84(5):489–497.
123. Semeraro F, Cancarini A, Morescalchi F, Romano M, dell'Omo R, Ruggeri G, Agnifili L, Costagliola C. 2014. Serum and intraocular concentrations of erythropoietin and vascular endothelial growth factor in patients with type 2 diabetes and proliferative retinopathy. Diabetes Metab 40(6):445–451.
124. Semeraro F, Cancarini A, dell'Omo R, Rezzola S, Romano M, Costagliola C. 2015. Diabetic retinopathy: Vascular and inflammatory disease. J Diabetes Res 2015:582060.
125. Sennlaub F, Valamanesh F, Vazquez-Tello A, El-Asrar A, Checchin D, Brault S, Gobeil F, Beauchamp M, Mwaikambo B, Courtois Y, Geboes K, Varma D, Lachapelle P, Ong H, Behar-Cohen F, Chemtob S. 2003. Cyclooxygenase-2 in human and experimental ischemic proliferative retinopathy. Circulation 108(2):198–204.
126. Serhan C, Brain S, Buckley C, Gilroy D, Haslett C, O'Neill L, Perretti M, Rossi A, Wallace J. 2007. Resolution of inflammation: State of the art, definitions and terms. Faseb j 21(2):325–332.
127. Shaw JE, Sicree RA, Zimmet PZ. 2010. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 87(1):4–14.
128. Sibal L, Aldibbiat A, Agarwal S, Mitchell G, Oates C, Razvi S, Weaver J, Shaw J, Home P. 2009. Circulating endothelial progenitor cells, endothelial function, carotid intima-media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria. Diabetologia 52(8):1464–1473.
129. Simo-Servat O, Hernandez C, Simo R. 2013. Genetics in diabetic retinopathy: Current concepts and new insights. Curr Genomics 14(5):289–299.
130. Stewart MW. 2012. Anti-vascular endothelial growth factor drug treatment of diabetic macular edema: The evolution continues. Curr Diabetes Rev 8(4):237–246.
131. Stewart MW. 2014. Anti-VEGF therapy for diabetic macular edema. Curr Diab Rep 14(8):510.
132. Stitt AW. 2003. The role of advanced glycation in the pathogenesis of diabetic retinopathy. Exp Mol Pathol 75(1):95–108.
133. Sulaiman RS, Basavarajappa HD, Corson TW. 2014. Natural product inhibitors of ocular angiogenesis. Exp Eye Res 129:161–171.
134. Tang J, Kern TS. 2011. Inflammation in diabetic retinopathy. Prog Retin Eye Res 30(5):343–358.
135. Tarr JM, Kaul K, Chopra M, Kohner E, Chibber R. 2013. Pathophysiology of diabetic retinopathy. ISRN Ophthalmol 2013:343560.
136. Tepper O, Galiano R, Capla J, Kalka C, Gagne P, Jacobowitz G, Levine J, Gurtner G. 2002. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 106(22):2781–2786.
137. Tomic M, Ljubic S, Kastelan S. 2013. The role of inflammation and endothelial dysfunction in the pathogenesis of diabetic retinopathy. Coll Antropol 37(Suppl 1):51–57.
138. Tsutsumi C, Sonoda K, Egashira K, Qiao H, Hisatomi T, Nakao S, Ishibashi M, Charo I, Sakamoto T, Murata T, Ishibashi T. 2003. The critical role of ocular-infiltrating macrophages in the development of choroidal neovascularization. J Leukoc Biol 74(1):25–32.
139. Uckermann O, Kutzera F, Wolf A, Pannicke T, Reichenbach A, Wiedemann P, Wolf S, Bringmann A. 2005. The glucocorticoid triamcinolone acetonide inhibits osmotic swelling of retinal glial cells via stimulation of endogenous adenosine signaling. J Pharmacol Exp Ther 315(3):1036–1045.
140. Urbich C, Dimmeler S. 2004. Endothelial progenitor cells: Characterization and role in vascular biology. Circ Res 95(4):p. 343–p. 353.
141. Vaz F, Silva F, Henrique J. 2012. O que se entende por terapêutica combinadano tratamento da retinopatia diabética? 25 Perguntas e respostas: Retinopatia Diabética- novo paradigma de cuidados. Lisboa: Grupo de estudos da Retina.
142. Voronov E, Shouval D, Krelin Y, Cagnano E, Benharroch D, Iwakura Y, Dinarello C, Apte R. 2003. IL-1 is required for tumor invasiveness and angiogenesis. Proc Natl Acad Sci USA 100(5):2645–2650.
143. Wang J, Xu X, Elliott M, Zhu M, Le Y. 2010. Muller cell-derived VEGF is essential for diabetes-induced retinal inflammation and vascular leakage. Diabetes 59(9):2297–2305.
144. Wells J, Glassman A, Ayala A, Jampol L, Aiello L, Antoszyk A, Arnold-Bush B, Baker C, Bressler N, Browning D, Elman M, Ferris F, Friedman S, Melia M, Pieramici D, Sun J, Beck R. 2015. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med 372(13):1193–1203.
145. Wells J, Glassman A, Ayala A, Jampol L, Bressler N, Bressler S, Brucker A, Ferris F, Hampton G, Jhaveri C, Melia M, Beck R. 2016. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema: Two-Year results from a comparative effectiveness randomized clinical trial. Ophthalmology. in press.
146. Wild S, Roglic G, Green A, Sicree R, King H. 2004. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care 27(5):1047–1053.
147. Wilkinson CP, Ferris FL, 3rd, Klein R, Lee P, Agardh C, Davis M, Dills D, Kampik A, Pararajasegaram R, Verdaguer J. 2003. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 110(9):1677–1682.
148. Williams CS, Mann M, DuBois RN. 1999. The role of cyclooxygenases in inflammation, cancer, and development. Oncogene 18(55):7908–7916.
149. Williams R, Airey M, Baxter H, Forrester J, Kennedy-Martin T, Girach A. 2004. Epidemiology of diabetic retinopathy and macular oedema: A systematic review. Eye (Lond) 18(10):963–983.
150. Wirostko B, Wong TY, Simo R. 2008. Vascular endothelial growth factor and diabetic complications. Prog Retin Eye Res 27(6):608–621.
151. Wu L, Fernandez-Loaiza P, Sauma J, Hernandez-Bogantes E, Masis M. 2013. Classification of diabetic retinopathy and diabetic macular edema. World J Diabetes 4(6):290–294.
152. Yoshida A, Yoshida S, Ishibashi T, Kuwano M, Inomata H. 1999. Suppression of retinal neovascularization by the NF-kappaB inhibitor pyrrolidine dithiocarbamate in mice. Invest Ophthalmol Vis Sci 40(7):1624–1629.
153. Yun SH, Adelman RA. 2015. Recent developments in laser treatment of diabetic retinopathy. Middle East Afr J Ophthalmol 22(2):157–163.
154. Zhang SX, Ma JX. 2007. Ocular neovascularization: Implication of endogenous angiogenic inhibitors and potential therapy. Prog Retin Eye Res 26(1):1–37.
155. Zhang J, Gerhardinger C, Lorenzi M. 2002. Early complement activation and decreased levels of glycosylphosphatidylinositol-anchored complement inhibitors in human and experimental diabetic retinopathy. Diabetes 51(12):3499–3504.
156. Zheng L, Howell S, Hatala D, Huang K, Kern T. 2007. Salicylate-based anti-inflammatory drugs inhibit the early lesion of diabetic retinopathy. Diabetes 56(2):337–345.
157. Zijlstra A, Seandel M, Kupriyanova T, Partridge J, Madsen M, Hahn-Dantona E, Quigley P, Deryugina E. 2006. Proangiogenic role of neutrophil-like inflammatory heterophils during neovascularization induced by growth factors and human tumor cells. Blood 107(1):317–327.
158. Zong H, Ward M, Madden A, Yong P, Limb G, Curtis T, Stitt A. 2010. Hyperglycaemia-induced pro-inflammatory responses by retinal Muller glia are regulated by the receptor for advanced glycation end-products (RAGE). Diabetologia 53(12):2656–2666.
159. Zorena K. 2014. Anti-inflammatory therapy in diabetic retinopathy. Mediators Inflamm 2014:947896.