Oxidative stress, mitochondrial damage and diabetic retinopathy

Biochimica et Biophysica Acta - Molecular Basis of Disease

Volumn 1852, Issue 11, 2015, Pages 2474-2483

  Kowluru, Renu A ^a   Mishra, Manish ^a  

^a WAYNE STATE UNIVERSITY   (United States)

Author keywords

Diabetic retinopathy; Mitochondria; Oxidative Stress

Indexed keywords

ACETYLCYSTEINE; ALPHA TOCOPHEROL; ANTIOXIDANT; ASCORBIC ACID; BENFOTIAMINE; BETA CAROTENE; CAROTENOID; CURCUMIN; DOBESILATE CALCIUM; EPIGALLOCATECHIN GALLATE; GENISTEIN; GLUTATHIONE PEROXIDASE; GLUTATHIONE REDUCTASE; IMISOPASEM MANGANESE; MITOCHONDRIAL DNA; NICANARTINE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; PEROXYNITRITE; POLYPHENOL; PYCNOGENOL; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; SELENIUM; SUPEROXIDE; TEMPOL; THIOCTIC ACID; TROLOX C; UBIDECARENONE; XANTHOPHYLL; ZEAXANTHIN;

DIABETIC RETINOPATHY; DNA DAMAGE; DNA MODIFICATION; DNA TRANSCRIPTION; ELECTRON TRANSPORT; EPIGENETICS; HUMAN; METABOLIC DISORDER; MITOCHONDRION; MOLECULAR PATHOLOGY; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; REVIEW; TEA;

EID: 84940778049     PISSN: 09254439     EISSN: 1879260X     Source Type: Journal    
DOI: 10.1016/j.bbadis.2015.08.001     Document Type: Review

References (108)

1. Federation I.D. The IDF Diabetes Atlas 2014, 6th edition.
2. Frank R.N. Diabetic retinopathy. N. Engl. J. Med. 2004, 350:48-58.
3. Klein R., Lee K.E., Gangnon R.E., Klein B.E. The 25-year incidence of visual impairment in type 1 diabetes mellitus the wisconsin epidemiologic study of diabetic retinopathy. Ophthalmology 2010, 117:63-70.
4. Zheng Y., He M., Congdon N. The worldwide epidemic of diabetic retinopathy. Indian J. Ophthalmol. 2012, 60:428-431.
5. Provis J.M. Development of the primate retinal vasculature. Prog. Retin. Eye Res. 2001, 20:799-821.
6. Mizutani M., Kern T.S., Lorenzi M. Accelerated death of retinal microvascular cells in human and experimental diabetic retinopathy. J. Clin. Invest. 1996, 97:2883-2890.
7. Du Y., Veenstra A., Palczewski K., Kern T.S. Photoreceptor cells are major contributors to diabetes-induced oxidative stress and local inflammation in the retina. Proc. Natl. Acad. Sci. U. S. A. 2013, 110:16586-16591.
8. Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N. Engl. J. Med. 2005, 353:2643-2653.
9. Engerman R.L., Kern T.S. Progression of incipient diabetic retinopathy during good glycemic control. Diabetes 1987, 36:808-812.
10. Kowluru R.A. Effect of re-institution of good glycemic control on retinal oxidative stress and nitrative stress in diabetic rats. Diabetes 2003, 52:818-823.
11. Mishra M., Zhong Q., Kowluru R.A. Epigenetic modifications of Nrf2-mediated glutamate-cysteine ligase: implications for the development of diabetic retinopathy and the metabolic memory phenomenon associated with its continued progression. Free Radic. Biol. Med. 2014, 75C:129-139.
12. Mishra M., Zhong Q., Kowluru R.A. Epigenetic modifications of Keap1 regulate its interaction with the protective factor Nrf2 in the development of diabetic retinopathys. Invest. Ophthalmol. Vis. Sci. 2014, 55:7256-7265.
13. Santos J.M., Mishra M., Kowluru R.A. Posttranslational modification of mitochondrial transcription factor A in impaired mitochondria biogenesis: implications in diabetic retinopathy and metabolic memory phenomenon. Exp. Eye Res. 2014, 121:168-177.
14. Chew E.Y., Davis M.D., Danis R.P., Lovato J.F., Perdue L.H., Greven C., Genuth S., Goff D.C., Leiter L.A., Ismail-Beigi F., Ambrosius W.T. The effects of medical management on the progression of diabetic retinopathy in persons with type 2 diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study. Ophthalmology 2014, 121:2443-2451.
15. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 2005, 54:1615-1625.
16. Kowluru R.A., Chan P.S. Oxidative stress and diabetic retinopathy. Exp. Diabetes Res. 2007, 2007:43603.
17. Kowluru R.A., Kowluru A., Veluthakal R., Mohammad G., Syed I., Santos J.M., Mishra M. TIAM1-RAC1 signalling axis-mediated activation of NADPH oxidase-2 initiates mitochondrial damage in the development of diabetic retinopathy. Diabetologia 2014, 57:1047-1056.
18. Kowluru R.A., Santos J.M., Mishra M. Epigenetic modifications and diabetic retinopathy. Biomed. Res. Int. 2013, 2013:635284.
19. Stitt A.W. AGEs and diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2010, 51:4867-4874.
20. Ott C., Jacobs K., Haucke E., Navarrete Santos A., Grune T., Simm A. Role of advanced glycation end products in cellular signaling. Redox Biol. 2014, 2:411-429.
21. Stitt A.W. The role of advanced glycation in the pathogenesis of diabetic retinopathy. Exp. Mol. Pathol. 2003, 75:95-108.
22. Ramasamy R., Yan S.F., Schmidt A.M. Receptor for AGE (RAGE): signaling mechanisms in the pathogenesis of diabetes and its complications. Ann. N. Y. Acad. Sci. 2011, 1243:88-102.
23. Katakami N., Kaneto H., Takahara M., Matsuoka T.A., Imamura K., Ishibashi F., Kanda T., Kawai K., Osonoi T., Matsuhisa M., Kashiwagi A., Kawamori R., Shimomura I., Yamasaki Y. Aldose reductase C-106T gene polymorphism is associated with diabetic retinopathy in Japanese patients with type 2 diabetes. Diabetes Res. Clin. Pract. 2011, 92:e57-e60.
24. Sorbinil Retinopathy Trial Research Group A randomized trial of sorbinil, an aldose reductase inhibitor, in diabetic retinopathy. Arch. Ophthalmol. 1990, 108:1234-1244.
25. Geraldes P., Hiraoka-Yamamoto J., Matsumoto M., Clermont A., Leitges M., Marette A., Aiello L.P., Kern T.S., King G.L. Activation of PKC-delta and SHP-1 by hyperglycemia causes vascular cell apoptosis and diabetic retinopathy. Nat. Med. 2009, 15:1298-1306.
26. Davis M.D., Sheetz M.J., Aiello L.P., Milton R.C., Danis R.P., Zhi X., Girach A., Jimenez M.C., Vignati L., P.-D.S.Group Effect of ruboxistaurin on the visual acuity decline associated with long-standing diabetic macular edema. Invest. Ophthalmol. Vis. Sci. 2009, 50:1-4.
27. Du X., Matsumura T., Edelstein D., Rossetti L., Zsengeller Z., Szabo C., Brownlee M. Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells. J. Clin. Invest. 2003, 112:1049-1057.
28. Anderson R.E., Rapp L.M., Wiegand R.D. Lipid peroxidation and retinal degeneration. Curr. Eye Res. 1984, 3:223-227.
29. Du X.L., Edelstein D., Rossetti L., Fantus I.G., Goldberg H., Ziyadeh F., Wu J., Brownlee M. Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc. Natl. Acad. Sci. 2000, 97:12222-12226.
30. Kowluru A., Kowluru R.A. Phagocyte-like NADPH oxidase [Nox2] in cellular dysfunction in models of glucolipotoxicity and diabetes. Biochem. Pharmacol. 2014, 88:275-283.
31. Armstrong D., Al-Awadi F. Lipid peroxidation and retinopathy in streptozotocin-induced diabetes. Free Radic. Biol. Med. 1991, 11:433-436.
32. Kowluru R.A. Diabetes-induced elevations in retinal oxidative stress, protein kinase C and nitric oxide are inter-related. Acta Diabetol. 2001, 38:179-185.
33. Cutler R.G. Oxidative stress profiling: part I. Its potential importance in the optimization of human health. Ann. N. Y. Acad. Sci. 2005, 1055:93-135.
34. Kowluru R.A., Kern T.S., Engerman R.L. Abnormalities of retinal metabolism in diabetes or experimental galactosemia. IV. Antioxidant defense system. Free Radic. Biol. Med. 1997, 22:587-592.
35. Narayanan S.P., Rojas M., Suwanpradid J., Toque H.A., Caldwell R.W., Caldwell R.B. Arginase in retinopathy. Prog. Retin. Eye Res. 2013, 36:260-280.
36. Murphy M.P. How mitochondria produce reactive oxygen species. Biochem. J. 2009, 417:1-13.
37. Kowaltowski A.J., de Souza-Pinto N.C., Castilho R.F., Vercesi A.E. Mitochondria and reactive oxygen species. Free Radic. Biol. Med. 2009, 47:333-343.
38. Trumpower B.L. The protonmotive Q cycle. Energy transduction by coupling of proton translocation to electron transfer by the cytochrome bc1 complex. J. Biol. Chem. 1990, 265:11409-11412.
39. Kanwar M., Chan P.S., Kern T.S., Kowluru R.A. Oxidative damage in the retinal mitochondria of diabetic mice: possible protection by superoxide dismutase. Invest. Ophthalmol. Vis. Sci. 2007, 48:3805-3811.
40. Santos J.M., Tewari S., Lin J.Y., Kowluru R.A. Interrelationship between activation of matrix metalloproteinases and mitochondrial dysfunction in the development of diabetic retinopathy. Biochem. Biophys. Res. Commun. 2013, 438:760-764.
41. Kowluru R.A., Mohammad G., dos Santos J.M., Zhong Q. Abrogation of MMP-9 gene protects against the development of retinopathy in diabetic mice by preventing mitochondrial damage. Diabetes 2011, 60:3023-3033.
42. Frey R.S., Ushio-Fukai M., Malik A.B. NADPH oxidase-dependent signaling in endothelial cells: role in physiology and pathophysiology. Antioxid. Redox Signal. 2009, 11:791-810.
43. Miller A.G., Smith D.G., Bhat M., Nagaraj R.H. Glyoxalase I is critical for human retinal capillary pericyte survival under hyperglycemic conditions. J. Biol. Chem. 2006, 281:11864-11871.
44. Cowell R.M., Russell J.W. Nitrosative injury and antioxidant therapy in the management of diabetic neuropathy. J. Investig. Med. 2004, 52:33-44.
45. Gopalkrishna R., Janken S. Protein kinase C signalling and oxidative stress. Free Radic. Biol. Med. 2000, 28:1349-1361.
46. Nakamura M., Barber A.J., Antonetti D.A., LaNoue K.F., Robinson K.A., Buse M.G., Gardner T.W. Excessive hexosamines block the neuroprotective effect of insulin and induce apoptosis in retinal neurons. J. Biol. Chem. 2001, 47:43748-43755.
47. Kern T.S. Contributions of inflammatory processes to the development of the early stages of diabetic retinopathy. Exp. Diabetes Res. 2007, 2007:95103.
48. Romeo G., Liu W.H., Asnaghi V., Kern T.S., Lorenzi M. Activation of nuclear factor-kappaB induced by diabetes and high glucose regulates a proapoptotic program in retinal pericytes. Diabetes 2002, 51:2241-2248.
49. Kowluru R.A., Koppolu P., Chakrabarti S., Chen S. Diabetes-induced activation of nuclear transcriptional factor in the retina, and its inhibition by antioxidants. Free Radic. Res. 2003, 37:1169-1180.
50. Chang C.K., LoCicero J. Overexpressed nuclear factor [kappa]B correlates with enhanced expression of interleukin-1[beta] and inducible nitric oxide synthase in aged murine lungs to endotoxic stress. Ann. Thorac. Surg. 2004, 77:1222-1227.
51. Vassilakopoulos T., Karatza M.-H., Katsaounou P., Kollintza A., Zakynthinos S., Roussos C. Antioxidants attenuate the plasma cytokine response to exercise in humans. J. Appl. Physiol. 2003, 94:1025-1032.
52. Kowluru R.A., Odenbach S. Role of interleukin-1beta in the development of retinopathy in rats: effect of antioxidants. Invest. Ophthalmol. Vis. Sci. 2004, 45:4161-4166.
53. Kowluru R.A., Tang J., Kern T.S. Abnormalities of retinal metabolism in diabetes and experimental galactosemia. VII. Effect of long-term administration of antioxidants on the development of retinopathy. Diabetes 2001, 50:1938-1942.
54. Candas D., Li J.J. MnSOD in oxidative stress response-potential regulation via mitochondrial protein influx. Antioxid. Redox Signal. 2014, 20:1599-1617.
55. Finley L.W., Haigis M.C. The coordination of nuclear and mitochondrial communication during aging and calorie restriction. Ageing Res. Rev. 2009, 8:173-188.
56. Whelan S.P., Zuckerbraun B.S. Mitochondrial signaling: forwards, backwards, and in between. Oxidative Med. Cell. Longev. 2013, 2013:351613.
57. Kowluru R.A., Kowluru A., Mishra M., Kumar B. Oxidative stress and epigenetic modifications in the pathogenesis of diabetic retinopathy. Prog. Retin. Eye Res. 2015, 48:40-61.
58. Perrone L., Matrone C., Singh L.P. Epigenetic modifications and potential new treatment targets in diabetic retinopathy. J. Ophthalmol. 2014, 2014:789120.
59. Kowluru R.A., Abbas S.N. Diabetes-induced mitochondrial dysfunction in the retina. Investig. Ophthalmol. Vis. Sci. 2003, 44:5327-5334.
60. Mishra M., Kowluru R.A. Retinal mitochondrial DNA mismatch repair in the development of diabetic retinopathy, and its continued progression after termination of hyperglycemia. Invest. Ophthalmol. Vis. Sci. 2014, 55:6960-6967.
61. Santos J.M., Tewari S., Kowluru R.A. A compensatory mechanism protects retinal mitochondria from initial insult in diabetic retinopathy. Free Radic. Biol. Med. 2012, 53:1729-1737.
62. Daiber A. Redox signaling (cross-talk) from and to mitochondria involves mitochondrial pores and reactive oxygen species. Biochim. Biophys. Acta 2010, 1797:897-906.
63. Echtay K.S., Esteves T.C., Pakay J.L., Jekabsons M.B., Lambert A.J., Portero-Otin M., Pamplona R., Vidal-Puig A.J., Wang S., Roebuck S.J., Brand M.D. A signalling role for 4-hydroxy-2-nonenal in regulation of mitochondrial uncoupling. EMBO J. 2003, 22:4103-4110.
64. Brondani L.A., de Souza B.M., Duarte G.C., Kliemann L.M., Esteves J.F., Marcon A.S., Gross J.L., Canani L.H., Crispim D. The UCP1-3826A/G polymorphism is associated with diabetic retinopathy and increased UCP1 and MnSOD2 gene expression in human retina. Invest. Ophthalmol. Vis. Sci. 2012, 53:7449-7457.
65. Scarpulla R.C. Nucleus-encoded regulators of mitochondrial function: integration of respiratory chain expression, nutrient sensing and metabolic stress. Biochim. Biophys. Acta 2012, 1819:1088-1097.
66. Madsen-Bouterse S., Zhong Q., Mohammad G., Ho Y.S., Kowluru R.A. Oxidative damage of mitochondrial DNA in diabetes, and its protection by manganese superoxide dismutase. Free Radic. Res. 2010, 44:313-321.
67. Santos R.X., Correia S.C., Zhu X., Smith M.A., Moreira P.I., Castellani R.J., Nunomura A., Perry G. Mitochondrial DNA oxidative damage and repair in aging and Alzheimer's disease. Antioxid. Redox Signal. 2013, 18:2444-2457.
68. Zhong Q., Kowluru R.A. Diabetic retinopathy and damage to mitochondrial structure and transport machinery. Investig. Ophthalmol. Vis. Sci. 2011, 52:8739-8746.
69. Tewari S., Santos J.M., Kowluru R.A. Damaged mitochondrial DNA replication system and the development of diabetic retinopathy. Antioxid. Redox Signal. 2012, 17:492-504.
70. Tewari S., Zhong Q., Santos J.M., Kowluru R.A. Mitochondria DNA replication and DNA methylation in the metabolic memory associated with continued progression of diabetic retinopathy. Investig. Ophthalmol. Vis. Sci. 2012, 53:4881-4888.
71. Santos J.M., Tewari S., Goldberg A.F.X., Kowluru R.A. Mitochondria biogenesis and the development of diabetic retinopathy. Free Radic. Biol. Med. 2011, 51:1849-1860.
72. Martin-Subero J.I. How epigenomics brings phenotype into being. Pediatr. Endocrinol. Rev. 2011, 9:506-510.
73. Reddy M.A., Zhang E., Natarajan R. Epigenetic mechanisms in diabetic complications and metabolic memory. Diabetologia 2015, 58:443-455.
74. Zhong Q., Kowluru R.A. Epigenetic changes in mitochondrial superoxide dismutase in the retina and the development of diabetic retinopathy. Diabetes 2011, 60:1304-1313.
75. Syreeni A., El-Osta A., Forsblom C., Sandholm N., Parkkonen M., Tarnow L., Parving H.H., McKnight A.J., Maxwell A.P., Cooper M.E. Genetic examination of SETD7 and SUV39H1/H2 methyltransferases and the risk of diabetes complications in patients with type 1 diabetes. Diabetes 2011, 60:3073-3080.
76. Kadiyala C.S., Zheng L., Du Y., Yohannes E., Kao H.Y., Miyagi M., Kern T.S. Acetylation of retinal histones in diabetes increases inflammatory proteins: effects of minocycline and manipulation of histone acetyltransferase (HAT) and histone deacetylase (HDAC). J. Biol. Chem. 2012, 287:25869-25880.
77. Zhong Q., Mishra M., Kowluru R.A. Transcription factor Nrf2-mediated antioxidant defense system in the development of diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2013, 54:3941-3948.
78. Zhong Q., Kowluru R.A. Regulation of matrix metalloproteinase-9 by epigenetic modifications and the development of diabetic retinopathy. Diabetes 2013, 62:2559-2568.
79. Gravina S., Vijg J. Epigenetic factors in aging and longevity. Pflugers Arch. 2010, 459:247-258.
80. Iacobazzi V., Castegna A., Infantino V., Andria G. Mitochondrial DNA methylation as a next-generation biomarker and diagnostic tool. Mol. Genet. Metab. 2013, 110:25-34.
81. Mishra M., Kowluru R.A. Role of mitochondrial DNA methylation in the development of diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2015, 56:5133-5142.
82. Mastropasqua R., Toto L., Cipollone F., Santovito D., Carpineto P., Mastropasqua L. Role of microRNAs in the modulation of diabetic retinopathy. Prog. Retin. Eye Res. 2014, 43C:92-107.
83. Silva V.A., Polesskaya A., Sousa T.A., Corrêa V.M., André N.D., Reis R.I., Kettelhut I.C., Harel-Bellan A., De Lucca F.L. Expression and cellular localization of microRNA-29b and RAX, an activator of the RNA-dependent protein kinase (PKR), in the retina of streptozotocin-induced diabetic rats. Mol. Vis. 2011, 17:2228-2240.
84. Kowluru R.A., Santos J.M., Zhong Q. Sirt1, a negative regulator of matrix metalloproteinase-9 in diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2014, 55:5653-5660.
85. Silva K.C., Rosales M.A., Hamassaki D.E., Saito K.C., Faria A.M., Ribeiro P.A., Faria J.B., Faria J.M. Green tea is neuroprotective in diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2013, 54:1325-1336.
86. Kowluru R.A., Odenbach S. Effect of long-term administration of alpha lipoic acid on retinal capillary cell death and the development of retinopathy in diabetic rats. Diabetes 2004, 53:3233-3238.
87. Tarallo S., Beltramo E., Berrone E., Porta M. Human pericyte-endothelial cell interactions in co-culture models mimicking the diabetic retinal microvascular environment. Acta Diabetol. 2012, 49:S141-S151.
88. Hammes H.P., Du X., Edelstein D., Taguchi T., Matsumura T., Ju Q., Lin J., Bierhaus A., Nawroth P., Hannak D., Neumaier M., Bergfeld R., Giardino I., Brownlee M. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat. Med. 2003, 9:294-299.
89. Hammes H.P., Bartmann A., Engel L., Wulfroth P. Antioxidant treatment of experimental diabetic retinopathy in rats with nicanartine. Diabetologia 1997, 40:629-634.
90. Ansari N.H., Zhang W., Fulep E., Mansour A. Prevention of pericyte loss by Trolox in diabetic rat retina. J. Toxicol. Environ. Health 1998, 24:467-475.
91. Kowluru R.A., Zhong Q., Santos J.M., Thandampallayam M., Putt D., Gierhart D.L. Beneficial effects of the nutritional supplements on the development of diabetic retinopathy. Nutr. Metab. (Lond.) 2014, 11:8.
92. Kowluru R.A., Kanwar M., Chan P.S., Zhang J.P. Inhibition of retinopathy and retinal metabolic abnormalities in diabetic rats with AREDS-based micronutrients. Arch. Ophthalmol. 2008, 126:1266-1272.
93. Coppey L.J., Gellett J.S., Davidson E.P., Dunlap J.A., Lund D.D., Salvemini D., Yorek M.A. Effect of M40403 treatment of diabetic rats on endoneurial blood flow, motor nerve conduction velocity and vascular function of epineurial arterioles of the sciatic nerve. Br. J. Pharmacol. 2001, 134:21-29.
94. Kowluru R.A., Kanwar M. Effect of curcumin on retinal oxidative stress and inflammation in diabetes. Nutr. Metab. (Lond.) 2007, 4:1-8.
95. Kowluru R.A., Menon B., Gierhart D. Beneficial effect of zeaxanthin on retinal metabolic abnormalities in diabetic rat. Investig. Ophthalmol. Vis. Sci. 2008, 49:1645-1651.
96. Sugawara R., Hikichi T., Kitaya N., Mori F., Nagaoka T., Yoshida A., Szabo C. Peroxynitrite decomposition catalyst, FP15, and poly(ADP-ribose) polymerase inhibitor, PJ34, inhibit leukocyte entrapment in the retinal microcirculation of diabetic rats. Curr. Eye Res. 2004, 29.
97. Zheng L., Szabo C., Kern T.S. Poly(ADP-ribose) polymerase is involved in the development of diabetic retinopathy via regulation of nuclear factor-kappaB. Diabetes 2004, 53:2960-2967.
98. Bursell S.E., Clermont A.C., Aiello L.P., Aiello L.M., Schlossman D.K., Feener E.P., L.L., King G.L. High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes. Diabetes Care 1999, 22:1245-1251.
99. Nebbioso M., Federici M., Rusciano D., Evangelista M., Pescosolido N. Oxidative stress in preretinopathic diabetes subjects and antioxidants. Diabetes Technol. Ther. 2012, 14:257-263.
100. Garay R.P., Hannaert P., Chiavaroli C. Calcium dobesilate in the treatment of diabetic retinopathy. Treat. Endocrinol. 2005, 4:221-232.
101. Spadea L., Balestrazzi E. Treatment of vascular retinopathies with Pycnogenol. Phytother. Res. 2001, 15:219-223.
102. Chous A.P., Richer S.P., Gerson J.D., Kowluru R.A. The Diabetes Visual Function Supplement Study (DiVFuSS). Br. J. Ophthalmol. 2015, (Epub ahead of print).
103. Millen A.E., Klein R., Folsom A.R., Stevens J., Palta M., Mares J.A. Relation between intake of vitamins C and E and risk of diabetic retinopathy in the Atherosclerosis Risk in Communities Study. Am. J. Clin. Nutr. 2004, 79:865-873.
104. Mayer-Davis E.J., Bell R.A., Reboussin B.A., Rushing J., Marshall J.A., Hamman R.F. Antioxidant nutrient intake and diabetic retinopathy: the San Luis Vally diabetes study. Ophthalmology 1998, 105:2264-2270.
105. Pearson P., Lewis S.A., Britton J., Young I.S., Fogarty A. The pro-oxidant activity of high-dose vitamin E supplements in vivo. BioDrugs 2006, 20:271-273.
106. Choi K.C., Jung M.G., Lee Y.H., Yoon J.C., Kwon S.H., Kang H.B., Kim M.J., Cha J.H., Kim Y.J., Jun W.J., Lee J.M., Yoon H.G. Epigallocatechin-3-gallate, a histone acetyltransferase inhibitor, inhibits EBV-induced B lymphocyte transformation via suppression of RelA acetylation. Cancer Res. 2009, 69:583-592.
107. Majid S., Dar A.A., Ahmad A.E., Hirata H., Kawakami K., Shahryari V., Saini S., Tanaka Y., Dahiya A.V., Khatri G., Dahiya R. BTG3 tumor suppressor gene promoter demethylation, histone modification and cell cycle arrest by genistein in renal cancer. Carcinogenesis 2009, 30:662-670.
108. Eglen R.M., Reisine T. Screening for compounds that modulate epigenetic regulation of the transcriptome: an overview. J. Biomol. Screen. 2011, 16:1137-1152.