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Aldo-Keto Reductases: Multifunctional Proteins as Therapeutic Targets in Diabetes and Inflammatory Disease

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Alcohol and Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1032))

Abstract

Aldose reductase (AR) is an NADPH-dependent aldo-keto reductase that has been shown to be involved in the pathogenesis of several blinding diseases such as uveitis, diabetic retinopathy (DR) and cataract. However, possible mechanisms linking the action of AR to these diseases are not well understood. As DR and cataract are among the leading causes of blindness in the world, there is an urgent need to explore therapeutic strategies to prevent or delay their onset. Studies with AR inhibitors and gene-targeted mice have demonstrated that the action of AR is also linked to cancer onset and progression. In this review we examine possible mechanisms that relate AR to molecular signaling cascades and thus explain why AR inhibition is an effective strategy against colon cancer as well as diseases of the eye such as uveitis, cataract, and retinopathy.

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References

  1. Bohren KM, Bullock B, Wermuth B, Gabbay KH (1989) The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases. J Biol Chem 264(16):9547–9551

    CAS  PubMed  Google Scholar 

  2. Iwata N, Inazu N, Satoh T (1989) The purification and characterization of NADPH-dependent carbonyl reductase from rat ovary. Prog Clin Biol Res 290:307–321

    CAS  PubMed  Google Scholar 

  3. Penning TM, Burczynski ME, Jez JM, Hung CF, Lin HK, Ma H, Moore M, Palackal N, Ratnam K (2000) Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones. Biochem J 351(Pt 1):67–77

    CAS  PubMed Central  PubMed  Google Scholar 

  4. Komoto J, Yamada T, Watanabe K, Takusagawa F (2004) Crystal structure of human prostaglandin F synthase (AKR1C3). Biochemistry 43(8):2188–2198

    Article  CAS  PubMed  Google Scholar 

  5. Hyndman D, Bauman DR, Heredia VV, Penning TM (2003) The aldo-keto reductase superfamily homepage. Chem Biol Interact 143–144:621–631

    Article  CAS  PubMed  Google Scholar 

  6. Jez JM, Bennett MJ, Schlegel BP, Lewis M, Penning TM (1997) Comparative anatomy of the aldo-keto reductase superfamily. Biochem J 326(Pt 3):625–636

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Barski OA, Gabbay KH, Bohren KM (1999) Characterization of the human aldehyde reductase gene and promoter. Genomics 60(2):188–198

    Article  CAS  PubMed  Google Scholar 

  8. Hayman S, Kinoshita JH (1965) Isolation and properties of lens aldose reductase. J Biol Chem 240:877–882

    CAS  PubMed  Google Scholar 

  9. Bauman DR, Steckelbroeck S, Penning TM (2004) The roles of aldo-keto reductases in steroid hormone action. Drug News Perspect 17(9):563–578

    Article  CAS  PubMed  Google Scholar 

  10. Sakuma M, Kametani S, Akanuma H (1998) Purification and some properties of a hepatic NADPH-dependent reductase that specifically acts on 1,5-anhydro-D-fructose. J Biochem 123(1):189–193

    Article  CAS  PubMed  Google Scholar 

  11. Penning TM (2015) The aldo-keto reductases (AKRs): overview. Chem Biol Interact 234:236–246

    Article  CAS  PubMed  Google Scholar 

  12. Karin M, Lin A (2002) NF-kappaB at the crossroads of life and death. Nat Immunol 3(3):221–227

    Article  CAS  PubMed  Google Scholar 

  13. Hoffmann A, Baltimore D (2006) Circuitry of nuclear factor kappaB signaling. Immunol Rev 210:171–186

    Article  PubMed  Google Scholar 

  14. Baldwin AS Jr (1996) The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol 14:649–683

    Article  CAS  PubMed  Google Scholar 

  15. Sheppard KA, Phelps KM, Williams AJ, Thanos D, Glass CK, Rosenfeld MG, Gerritsen ME, Collins T (1998) Nuclear integration of glucocorticoid receptor and nuclear factor-kappaB signaling by CREB-binding protein and steroid receptor coactivator-1. J Biol Chem 273(45):29291–29294

    Article  CAS  PubMed  Google Scholar 

  16. Sheppard KA, Rose DW, Haque ZK, Kurokawa R, McInerney E, Westin S, Thanos D, Rosenfeld MG, Glass CK, Collins T (1999) Transcriptional activation by NF-kappaB requires multiple coactivators. Mol Cell Biol 19(9):6367–6378

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Chen LF, Mu Y, Greene WC (2002) Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-kappaB. EMBO J 21(23):6539–6548

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, Mayo MW (2004) Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J 23(12):2369–2380

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Ramana KV, Fadl AA, Tammali R, Reddy ABM, Chopra AK, Srivastava SK (2006) Aldose reductase mediates the lipopolysaccharide-induced release of inflammatory mediators in RAW264.7 murine macrophages. J Biol Chem 281(44):33019–33029

    Article  CAS  PubMed  Google Scholar 

  20. Srivastava S, Dixit BL, Cai J, Sharma S, Hurst HE, Bhatnagar A, Srivastava SK (2000) Metabolism of lipid peroxidation product, 4-hydroxynonenal (HNE) in rat erythrocytes: role of aldose reductase. Free Radic Biol Med 29(7):642–651

    Article  CAS  PubMed  Google Scholar 

  21. Vander Jagt DL, Kolb NS, Vander Jagt TJ, Chino J, Martinez FJ, Hunsaker LA, Royer RE (1995) Substrate specificity of human aldose reductase: identification of 4-hydroxynonenal as an endogenous substrate. Biochim Biophys Acta 1249(2):117–126

    Article  PubMed  Google Scholar 

  22. Maccari R, Ottana R (2015) Targeting aldose reductase for the treatment of diabetes complications and inflammatory diseases: new insights and future directions. J Med Chem 58(5):2047–2067

    Article  CAS  PubMed  Google Scholar 

  23. Srivastava SK, Ramana KV, Bhatnagar A (2005) Role of aldose reductase and oxidative damage in diabetes and the consequent potential for therapeutic options. Endocr Rev 26(3):380–392

    Article  CAS  PubMed  Google Scholar 

  24. Ramana KV (2011) Aldose reductase: new insights for an old enzyme. Biomol Concepts 2(1–2):103–114

    CAS  PubMed Central  PubMed  Google Scholar 

  25. Ramana KV, Friedrich B, Srivastava S, Bhatnagar A, Srivastava SK (2004) Activation of nuclear factor-kappaB by hyperglycemia in vascular smooth muscle cells is regulated by aldose reductase. Diabetes 53(11):2910–2920

    Article  CAS  PubMed  Google Scholar 

  26. Evans JL, Goldfine ID, Maddux BA, Grodsky GM (2002) Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev 23(5):599–622

    Article  CAS  PubMed  Google Scholar 

  27. Ramana KV, Friedrich B, Tammali R, West MB, Bhatnagar A, Srivastava SK (2005) Requirement of aldose reductase for the hyperglycemic activation of protein kinase C and formation of diacylglycerol in vascular smooth muscle cells. Diabetes 54(3):818–829

    Article  CAS  PubMed  Google Scholar 

  28. Shen W, Gao Y, Lu B, Zhang Q, Hu Y, Chen Y (2014) Negatively regulating TLR4/NF-kappaB signaling via PPARalpha in endotoxin-induced uveitis. Biochim Biophys Acta 1842(7):1109–1120

    Article  CAS  PubMed  Google Scholar 

  29. Kalariya NM, Shoeb M, Ansari NH, Srivastava SK, Ramana KV (2012) Antidiabetic drug metformin suppresses endotoxin-induced uveitis in rats. Invest Ophthalmol Vis Sci 53(7):3431–3440

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Lustig MJ, Cunningham ET Jr (2003) Use of immunosuppressive agents in uveitis. Curr Opin Ophthalmol 14(6):399–412

    Article  PubMed  Google Scholar 

  31. Cunningham ET Jr, Wender JD (2010) Practical approach to the use of corticosteroids in patients with uveitis. Can J Ophthalmol Journal canadien d’ophtalmologie 45(4):352–358

    Article  PubMed  Google Scholar 

  32. Sadiq MA, Agarwal A, Hassan M, Afridi R, Sarwar S, Soliman MK, Do DV, Nguyen QD (2015) Therapies in development for non-infectious Uveitis. Curr Mol Med 15(6):565–577

    Article  CAS  PubMed  Google Scholar 

  33. Vermeulen L, De Wilde G, Notebaert S, Vanden Berghe W, Haegeman G (2002) Regulation of the transcriptional activity of the nuclear factor-kappaB p65 subunit. Biochem Pharmacol 64(5–6):963–970

    Article  CAS  PubMed  Google Scholar 

  34. Ceolotto G, De Kreutzenberg SV, Cattelan A, Fabricio AS, Squarcina E, Gion M, Semplicini A, Fadini GP, Avogaro A (2014) Sirtuin 1 stabilization by HuR represses TNF-alpha- and glucose-induced E-selectin release and endothelial cell adhesiveness in vitro: relevance to human metabolic syndrome. Clin Sci 127(7):449–461

    Article  CAS  Google Scholar 

  35. Petrash JM (2004) All in the family: aldose reductase and closely related aldo-keto reductases. Cell Mol Life Sci 61(7–8):737–749

    Article  CAS  PubMed  Google Scholar 

  36. Ramana KV, Fadl AA, Tammali R, Reddy AB, Chopra AK, Srivastava SK (2006) Aldose reductase mediates the lipopolysaccharide-induced release of inflammatory mediators in RAW264.7 murine macrophages. J Biol Chem 281(44):33019–33029

    Article  CAS  PubMed  Google Scholar 

  37. Ramana KV, Reddy AB, Tammali R, Srivastava SK (2007) Aldose reductase mediates endotoxin-induced production of nitric oxide and cytotoxicity in murine macrophages. Free Radic Biol Med 42(8):1290–1302

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Ramana KV, Srivastava SK (2006) Mediation of aldose reductase in lipopolysaccharide-induced inflammatory signals in mouse peritoneal macrophages. Cytokine 36(3–4):115–122

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Chang KC, Laffin B, Ponder J, Enzsoly A, Nemeth J, Labarbera DV, Petrash JM (2013) Beta-glucogallin reduces the expression of lipopolysaccharide-induced inflammatory markers by inhibition of aldose reductase in murine macrophages and ocular tissues. Chem Biol Interact 202(1–3):283–287

    Article  CAS  PubMed  Google Scholar 

  40. Chang KC, Ponder J, Labarbera DV, Petrash JM (2014) Aldose reductase inhibition prevents endotoxin-induced inflammatory responses in retinal microglia. Invest Ophthalmol Vis Sci 55(5):2853–2861

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Bhatnagar A, Srivastava SK (1992) Aldose reductase: congenial and injurious profiles of an enigmatic enzyme. Biochem Med Metab Biol 48(2):91–121

    Article  CAS  PubMed  Google Scholar 

  42. Sheetz MJ, King GL (2002) Molecular understanding of hyperglycemia’s adverse effects for diabetic complications. JAMA 288(20):2579–2588

    Article  CAS  PubMed  Google Scholar 

  43. Lou MF (2003) Redox regulation in the lens. Prog Retin Eye Res 22(5):657–682

    Article  CAS  PubMed  Google Scholar 

  44. Vedantham S, Ananthakrishnan R, Schmidt AM, Ramasamy R (2012) Aldose reductase, oxidative stress and diabetic cardiovascular complications. Cardiovasc Hematol Agents Med Chem 10(3):234–240

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Koya D, King GL (1998) Protein kinase C activation and the development of diabetic complications. Diabetes 47(6):859–866

    Article  CAS  PubMed  Google Scholar 

  46. Kandarakis SA, Piperi C, Topouzis F, Papavassiliou AG (2014) Emerging role of advanced glycation-end products (AGEs) in the pathobiology of eye diseases. Prog Retin Eye Res 42:85–102

    Article  CAS  PubMed  Google Scholar 

  47. Sadowska-Bartosz I, Galiniak S, Bartosz G (2014) Kinetics of glycoxidation of bovine serum albumin by glucose, fructose and ribose and its prevention by food components. Molecules 19(11):18828–18849

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Ramana KV, Willis MS, White MD, Horton JW, DiMaio JM, Srivastava D, Bhatnagar A, Srivastava SK (2006) Endotoxin-induced cardiomyopathy and systemic inflammation in mice is prevented by aldose reductase inhibition. Circulation 114(17):1838–1846

    Article  CAS  PubMed  Google Scholar 

  49. Yagihashi S, Mizukami H, Ogasawara S, Yamagishi S, Nukada H, Kato N, Hibi C, Chung S, Chung S (2010) The role of the polyol pathway in acute kidney injury caused by hindlimb ischaemia in mice. J Pathol 220(5):530–541

    Article  PubMed  Google Scholar 

  50. Takahashi K, Mizukami H, Kamata K, Inaba W, Kato N, Hibi C, Yagihashi S (2012) Amelioration of acute kidney injury in lipopolysaccharide-induced systemic inflammatory response syndrome by an aldose reductase inhibitor, fidarestat. PLoS One 7(1):e30134

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Yadav UC, Srivastava SK, Ramana KV (2007) Aldose reductase inhibition prevents endotoxin-induced uveitis in rats. Invest Ophthalmol Vis Sci 48(10):4634–4642

    Article  PubMed  Google Scholar 

  52. Yadav UC, Shoeb M, Srivastava SK, Ramana KV (2011) Aldose reductase deficiency protects from autoimmune- and endotoxin-induced uveitis in mice. Invest Ophthalmol Vis Sci 52(11):8076–8085

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Di Filippo C, Zippo MV, Maisto R, Trotta MC, Siniscalco D, Ferraro B, Ferraraccio F, La Motta C, Sartini S, Cosconati S, Novellino E, Gesualdo C, Simonelli F, Rossi S, D’Amico M (2014) Inhibition of ocular aldose reductase by a new benzofuroxane derivative ameliorates rat endotoxic uveitis. Mediat Inflamm 2014:857958

    Google Scholar 

  54. Jaspan JB, Towle VL, Maselli R, Herold K (1986) Clinical studies with an aldose reductase inhibitor in the autonomic and somatic neuropathies of diabetes. Metab Clin Exp 35(4 Suppl 1):83–92

    Article  CAS  PubMed  Google Scholar 

  55. Green A, Jaspan J, Kavin H, Chung S, Schoenberg H (1987) Influence of long-term aldose reductase inhibitor therapy on autonomic dysfunction of urinary bladder, stomach and cardiovascular systems in diabetic patients. Diabetes Res Clin Pract 4(1):67–75

    Article  CAS  PubMed  Google Scholar 

  56. Roy TM, Broadstone VL, Peterson HR, Snider HL, Cyrus J, Fell R, Rothchild AH, Samols E, Pfeifer MA (1990) The effect of an aldose reductase inhibitor on cardiovascular performance in patients with diabetes mellitus. Diabetes Res Clin Pract 10(1):91–97

    Article  CAS  PubMed  Google Scholar 

  57. Kurata C, Okayama K, Wakabayashi Y, Shouda S, Mikami T, Tawarahara K, Sugiyama T (1997) Cardiac sympathetic neuropathy and effects of aldose reductase inhibitor in streptozotocin-induced diabetic rats. J Nucl Med Off Publ Soc Nucl Med 38(11):1677–1680

    CAS  Google Scholar 

  58. Utsunomiya K, Narabayashi I, Tamura K, Nakatani Y, Saika Y, Onishi S, Kariyone S (1998) Effects of aldose reductase inhibitor and vitamin B12 on myocardial uptake of iodine-123 metaiodobenzylguanidine in patients with non-insulin-dependent diabetes mellitus. Eur J Nucl Med 25(12):1643–1648

    Article  CAS  PubMed  Google Scholar 

  59. Ramasamy R, Oates PJ, Schaefer S (1997) Aldose reductase inhibition protects diabetic and nondiabetic rat hearts from ischemic injury. Diabetes 46(2):292–300

    Article  CAS  PubMed  Google Scholar 

  60. Ramasamy R, Liu H, Oates PJ, Schaefer S (1999) Attenuation of ischemia induced increases in sodium and calcium by the aldose reductase inhibitor zopolrestat. Cardiovasc Res 42(1):130–139

    Article  CAS  PubMed  Google Scholar 

  61. Tracey WR, Magee WP, Ellery CA, MacAndrew JT, Smith AH, Knight DR, Oates PJ (2000) Aldose reductase inhibition alone or combined with an adenosine A(3) agonist reduces ischemic myocardial injury. Am J Phys Heart Circ Phys 279(4):H1447–H1452

    CAS  Google Scholar 

  62. Hwang YC, Sato S, Tsai JY, Yan S, Bakr S, Zhang H, Oates PJ, Ramasamy R (2002) Aldose reductase activation is a key component of myocardial response to ischemia. FASEB J Off Publ Fed Am Soc Exp Biol 16(2):243–245

    CAS  Google Scholar 

  63. Shinmura K, Bolli R, Liu SQ, Tang XL, Kodani E, Xuan YT, Srivastava S, Bhatnagar A (2002) Aldose reductase is an obligatory mediator of the late phase of ischemic preconditioning. Circ Res 91(3):240–246

    Article  CAS  PubMed  Google Scholar 

  64. Hwang YC, Kaneko M, Bakr S, Liao H, Lu Y, Lewis ER, Yan S, Ii S, Itakura M, Rui L, Skopicki H, Homma S, Schmidt AM, Oates PJ, Szabolcs M, Ramasamy R (2004) Central role for aldose reductase pathway in myocardial ischemic injury. FASEB J Off Publ Fed Am Soc Exp Biol 18(11):1192–1199

    CAS  Google Scholar 

  65. Hwang YC, Shaw S, Kaneko M, Redd H, Marrero MB, Ramasamy R (2005) Aldose reductase pathway mediates JAK-STAT signaling: a novel axis in myocardial ischemic injury. FASEB J Off Publ Fed Am Soc Exp Biol 19(7):795–797

    CAS  Google Scholar 

  66. Kaiserova K, Srivastava S, Hoetker JD, Awe SO, Tang XL, Cai J, Bhatnagar A (2006) Redox activation of aldose reductase in the ischemic heart. J Biol Chem 281(22):15110–15120

    Article  CAS  PubMed  Google Scholar 

  67. Kaiserova K, Tang XL, Srivastava S, Bhatnagar A (2008) Role of nitric oxide in regulating aldose reductase activation in the ischemic heart. J Biol Chem 283(14):9101–9112

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Ananthakrishnan R, Li Q, Gomes T, Schmidt AM, Ramasamy R (2011) Aldose reductase pathway contributes to vulnerability of aging myocardium to ischemic injury. Exp Gerontol 46(9):762–767

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Tang WH, Cheng WT, Kravtsov GM, Tong XY, Hou XY, Chung SK, Chung SS (2010) Cardiac contractile dysfunction during acute hyperglycemia due to impairment of SERCA by polyol pathway-mediated oxidative stress. Am J Physiol Cell Physiol 299(3):C643–C653

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Sakamoto A, Sugamoto Y (2011) Identification of a novel aldose reductase-like gene upregulated in the failing heart of cardiomyopathic hamster. Mol Cell Biochem 353(1–2):275–281

    Article  CAS  PubMed  Google Scholar 

  71. Ho EC, Lam KS, Chen YS, Yip JC, Arvindakshan M, Yamagishi S, Yagihashi S, Oates PJ, Ellery CA, Chung SS, Chung SK (2006) Aldose reductase-deficient mice are protected from delayed motor nerve conduction velocity, increased c-Jun NH2-terminal kinase activation, depletion of reduced glutathione, increased superoxide accumulation, and DNA damage. Diabetes 55(7):1946–1953

    Article  CAS  PubMed  Google Scholar 

  72. Itagaki I, Shimizu K, Kamanaka Y, Ebata K, Kikkawa R, Haneda M, Shigeta Y (1994) The effect of an aldose reductase inhibitor (Epalrestat) on diabetic nephropathy in rats. Diabetes Res Clin Pract 25(3):147–154

    Article  CAS  PubMed  Google Scholar 

  73. Oates PJ (2010) Aldose reductase inhibitors and diabetic kidney disease. Curr Opin Investig Drugs 11(4):402–417

    CAS  PubMed  Google Scholar 

  74. Ahmed N, Thornalley PJ, Dawczynski J, Franke S, Strobel J, Stein G, Haik GM (2003) Methylglyoxal-derived hydroimidazolone advanced glycation end-products of human lens proteins. Invest Ophthalmol Vis Sci 44(12):5287–5292

    Article  PubMed  Google Scholar 

  75. Congdon NG, Friedman DS, Lietman T (2003) Important causes of visual impairment in the world today. JAMA 290(15):2057–2060

    Article  CAS  PubMed  Google Scholar 

  76. Kador PF, Randazzo J, Babb T, Koushik K, Takamura Y, Zhu W, Blessing K, Kompella UB (2007) Topical aldose reductase inhibitor formulations for effective lens drug delivery in a rat model for sugar cataracts. J Ocul Pharmacol Ther 23(2):116–123

    Article  CAS  PubMed  Google Scholar 

  77. Kawakubo K, Mori A, Sakamoto K, Nakahara T, Ishii K (2012) GP-1447, an inhibitor of aldose reductase, prevents the progression of diabetic cataract in rats. Biol Pharm Bull 35(6):866–872

    Article  CAS  PubMed  Google Scholar 

  78. Matsumoto T, Ono Y, Kuromiya A, Toyosawa K, Ueda Y, Bril V (2008) Long-term treatment with ranirestat (AS-3201), a potent aldose reductase inhibitor, suppresses diabetic neuropathy and cataract formation in rats. J Pharmacol Sci 107(3):340–348

    Article  CAS  PubMed  Google Scholar 

  79. Schalkwijk CG, Stehouwer CD, van Hinsbergh VW (2004) Fructose-mediated non-enzymatic glycation: sweet coupling or bad modification. Diabetes Metab Res Rev 20(5):369–382

    Article  CAS  PubMed  Google Scholar 

  80. Chang KC, Snow A, LaBarbera DV, Petrash JM (2015) Aldose reductase inhibition alleviates hyperglycemic effects on human retinal pigment epithelial cells. Chem Biol Interact 234:254–260

    Article  CAS  PubMed  Google Scholar 

  81. Hirata C, Nakano K, Nakamura N, Kitagawa Y, Shigeta H, Hasegawa G, Ogata M, Ikeda T, Sawa H, Nakamura K, Ienaga K, Obayashi H, Kondo M (1997) Advanced glycation end products induce expression of vascular endothelial growth factor by retinal Muller cells. Biochem Biophys Res Commun 236(3):712–715

    Article  CAS  PubMed  Google Scholar 

  82. Nguyen QD, Hatef E, Kayen B, Macahilig CP, Ibrahim M, Wang J, Shaikh O, Bodaghi B (2011) A cross-sectional study of the current treatment patterns in noninfectious uveitis among specialists in the United States. Ophthalmology 118(1):184–190

    Article  PubMed  Google Scholar 

  83. Tang J, Du Y, Petrash JM, Sheibani N, Kern TS (2013) Deletion of aldose reductase from mice inhibits diabetes-induced retinal capillary degeneration and superoxide generation. PLoS One 8(4):e62081

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. Yadav UC, Srivastava SK, Ramana KV (2012) Prevention of VEGF-induced growth and tube formation in human retinal endothelial cells by aldose reductase inhibition. J Diabetes Complicat 26(5):369–377

    Article  Google Scholar 

  85. Lehto S, Pyorala K, Miettinen H, Ronnemaa T, Palomaki P, Tuomilehto J, Laakso M (1994) Myocardial infarct size and mortality in patients with non-insulin-dependent diabetes mellitus. J Intern Med 236(3):291–297

    Article  CAS  PubMed  Google Scholar 

  86. Stone GW, Grines CL, Browne KF, Marco J, Rothbaum D, O'Keefe J, Hartzler GO, Overlie P, Donohue B, Chelliah N et al (1995) Predictors of in-hospital and 6-month outcome after acute myocardial infarction in the reperfusion era: the primary angioplasty in myocardial infarction (PAMI) trail. J Am Coll Cardiol 25(2):370–377

    Article  CAS  PubMed  Google Scholar 

  87. Greene DA, Lattimer SA, Sima AA (1987) Sorbitol, phosphoinositides, and sodium-potassium-ATPase in the pathogenesis of diabetic complications. N Engl J Med 316(10):599–606

    Article  CAS  PubMed  Google Scholar 

  88. Braunwald E, Bristow MR (2000) Congestive heart failure: fifty years of progress. Circulation 102(20 Suppl 4):IV14–IV23

    CAS  PubMed  Google Scholar 

  89. Tiwari S, Ndisang JF (2014) The role of obesity in cardiomyopathy and nephropathy. Curr Pharm Des 20(9):1409–1417

    Article  CAS  PubMed  Google Scholar 

  90. Fioretto P, Caramori ML, Mauer M (2008) The kidney in diabetes: dynamic pathways of injury and repair. The Camillo Golgi lecture 2007. Diabetologia 51(8):1347–1355

    Article  CAS  PubMed  Google Scholar 

  91. Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group, Nathan DM, Zinman B, Cleary PA, Backlund JY, Genuth S, Miller R, Orchard TJ (2009) Modern-day clinical course of type 1 diabetes mellitus after 30 years’ duration: the diabetes control and complications trial/epidemiology of diabetes interventions and complications and Pittsburgh epidemiology of diabetes complications experience (1983–2005). Arch Intern Med 169(14):1307–1316

    Article  Google Scholar 

  92. Kasajima H, Yamagishi S, Sugai S, Yagihashi N, Yagihashi S (2001) Enhanced in situ expression of aldose reductase in peripheral nerve and renal glomeruli in diabetic patients. Virchows Archiv Int J Pathol 439(1):46–54

    Article  CAS  Google Scholar 

  93. Morrisey K, Steadman R, Williams JD, Phillips AO (1999) Renal proximal tubular cell fibronectin accumulation in response to glucose is polyol pathway dependent. Kidney Int 55(6):2548–2572

    Article  CAS  PubMed  Google Scholar 

  94. Gabbay KH (1973) The sorbitol pathway and the complications of diabetes. N Engl J Med 288(16):831–836

    Article  CAS  PubMed  Google Scholar 

  95. Kador PF, Robison WG Jr, Kinoshita JH (1985) The pharmacology of aldose reductase inhibitors. Annu Rev Pharmacol Toxicol 25:691–714

    Article  CAS  PubMed  Google Scholar 

  96. Palsamy P, Subramanian S (2011) Resveratrol protects diabetic kidney by attenuating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via Nrf2-Keap1 signaling. Biochim Biophys Acta 1812(7):719–731

    Article  CAS  PubMed  Google Scholar 

  97. Forbes JM, Coughlan MT, Cooper ME (2008) Oxidative stress as a major culprit in kidney disease in diabetes. Diabetes 57(6):1446–1454

    Article  CAS  PubMed  Google Scholar 

  98. Yang JY, Tam WY, Tam S, Guo H, Wu X, Li G, Chau JF, Klein JD, Chung SK, Sands JM, Chung SS (2006) Genetic restoration of aldose reductase to the collecting tubules restores maturation of the urine concentrating mechanism. Am J Physiol Renal Physiol 291(1):F186–F195

    Article  CAS  PubMed  Google Scholar 

  99. Makino H, Kashihara N, Sugiyama H, Kanao K, Sekikawa T, Okamoto K, Maeshima Y, Ota Z, Nagai R (1996) Phenotypic modulation of the mesangium reflected by contractile proteins in diabetes. Diabetes 45(4):488–495

    Article  CAS  PubMed  Google Scholar 

  100. de Iongh RU, Wederell E, Lovicu FJ, McAvoy JW (2005) Transforming growth factor-beta-induced epithelial-mesenchymal transition in the lens: a model for cataract formation. Cells Tissues Organs 179(1–2):43–55

    Article  CAS  PubMed  Google Scholar 

  101. Huang P, Zhang Y, Jiang T, Zeng W, Zhang N (2010) Aldose reductase is a potent regulator of TGF-beta1 induced expression of fibronectin in human mesangial cells. Mol Biol Rep 37(7):3097–3103

    Article  CAS  PubMed  Google Scholar 

  102. Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freeman R, Malik RA, Maser RE, Sosenko JM, Ziegler D (2005) American Diabetes Association. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care 28(4):956–962

    Article  PubMed  Google Scholar 

  103. Jaspan JB (1995) Taking control of diabetes. Hosp Pract 30(10):55–62

    Article  CAS  Google Scholar 

  104. Zatalia SR, Sanusi H (2013) The role of antioxidants in the pathophysiology, complications, and management of diabetes mellitus. Acta Med Indones 45(2):141–147

    PubMed  Google Scholar 

  105. Zochodne DW (2007) Diabetes mellitus and the peripheral nervous system: manifestations and mechanisms. Muscle Nerve 36(2):144–166

    Article  CAS  PubMed  Google Scholar 

  106. Hotta N, Toyota T, Matsuoka K, Shigeta Y, Kikkawa R, Kaneko T, Takahashi A, Sugimura K, Koike Y, Ishii J, Sakamoto N, Group SNKDNS (2001) Clinical efficacy of fidarestat, a novel aldose reductase inhibitor, for diabetic peripheral neuropathy: a 52-week multicenter placebo-controlled double-blind parallel group study. Diabetes Care 24(10):1776–1782

    Article  CAS  PubMed  Google Scholar 

  107. Pan H, Jian F, Lin J, Chen N, Zhang C, Zhang Z, Ding Z, Wang Y, Cui L, Kimura J (2014) F-wave latencies in patients with diabetes mellitus. Muscle Nerve 49(6):804–808

    Article  PubMed  Google Scholar 

  108. Galuppo M, Giacoppo S, Bramanti P, Mazzon E (2014) Use of natural compounds in the management of diabetic peripheral neuropathy. Molecules 19(3):2877–2895

    Article  CAS  PubMed  Google Scholar 

  109. Possidente CJ, Tandan R (2009) A survey of treatment practices in diabetic peripheral neuropathy. Prim Care Diabetes 3(4):253–257

    Article  PubMed  Google Scholar 

  110. Tesfaye S, Vileikyte L, Rayman G, Sindrup SH, Perkins BA, Baconja M, Vinik AI, Boulton AJ (2011) Toronto expert panel on diabetic N. Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis, assessment and management. Diabetes Metab Res Rev 27(7):629–638

    Article  CAS  PubMed  Google Scholar 

  111. Suehiro K, Funao T, Fujimoto Y, Yamada T, Mori T, Nishikawa K (2013) Relationship between noradrenaline release in the locus coeruleus and antiallodynic efficacy of analgesics in rats with painful diabetic neuropathy. Life Sci 92(23):1138–1144

    Article  CAS  PubMed  Google Scholar 

  112. Mehrpour O (2013) Addiction and seizure ability of tramadol in high-risk patients. Indian J Anaesth 57(1):86–87

    Article  PubMed Central  PubMed  Google Scholar 

  113. Aloisi AM, Buonocore M, Merlo L, Galandra C, Sotgiu A, Bacchella L, Ungaretti M, Demartini L, Bonezzi C (2011) Chronic pain therapy and hypothalamic-pituitary-adrenal axis impairment. Psychoneuroendocrinology 36(7):1032–1039

    Article  CAS  PubMed  Google Scholar 

  114. Bhanot A, Shri R (2010) A comparative profile of methanol extracts of Allium cepa and Allium sativum in diabetic neuropathy in mice. Pharm Res 2(6):374–384

    Google Scholar 

  115. Selvarajah D, Gandhi R, Emery CJ, Tesfaye S (2010) Randomized placebo-controlled double-blind clinical trial of cannabis-based medicinal product (Sativex) in painful diabetic neuropathy: depression is a major confounding factor. Diabetes Care 33(1):128–130

    Article  PubMed  Google Scholar 

  116. Snedecor SJ, Sudharshan L, Cappelleri JC, Sadosky A, Mehta S, Botteman M (2014) Systematic review and meta-analysis of pharmacological therapies for painful diabetic peripheral neuropathy. Pain Pract Off J World Inst Pain 14(2):167–184

    Article  Google Scholar 

  117. Derry S, Sven-Rice A, Cole P, Tan T, Moore RA (2013) Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev 2:CD007393

    Google Scholar 

  118. Mou J, Paillard F, Turnbull B, Trudeau J, Stoker M, Katz NP (2013) Efficacy of Qutenza(R) (capsaicin) 8% patch for neuropathic pain: a meta-analysis of the Qutenza clinical trials database. Pain 154(9):1632–1639

    Article  CAS  PubMed  Google Scholar 

  119. Khalil H (2013) Painful diabetic neuropathy management. Int J Evid Based Healthc 11(1):77–79

    Article  PubMed  Google Scholar 

  120. Oka M, Kato N (2001) Aldose reductase inhibitors. J Enzym Inhib 16(6):465–473

    Article  CAS  PubMed  Google Scholar 

  121. Hotta N, Sakamoto N, Shigeta Y, Kikkawa R, Goto Y (1996) Clinical investigation of epalrestat, an aldose reductase inhibitor, on diabetic neuropathy in Japan: multicenter study. Diabetic neuropathy study group in Japan. J Diabetes Complicat 10(3):168–172

    Article  CAS  Google Scholar 

  122. Goto Y, Hotta N, Shigeta Y, Sakamoto N, Kito S, Matsuoka K, Takahashi A, Kikkawa R, Sakuma A (1993) A placebo-controlled double-blind study of epalrestat (ONO-2235) in patients with diabetic neuropathy. Diabet Med J Br Diabetic Assoc 10(Suppl 2):39S–43S

    Article  Google Scholar 

  123. Uchida K, Kigoshi T, Nakano S, Ishii T, Kitazawa M, Morimoto S (1995) Effect of 24 weeks of treatment with epalrestat, an aldose reductase inhibitor, on peripheral neuropathy in patients with non-insulin-dependent diabetes mellitus. Clin Ther 17(3):460–466

    Article  CAS  PubMed  Google Scholar 

  124. Schemmel KE, Padiyara RS, D’Souza JJ (2010) Aldose reductase inhibitors in the treatment of diabetic peripheral neuropathy: a review. J Diabetes Complicat 24(5):354–360

    Article  Google Scholar 

  125. Stavniichuk R, Shevalye H, Hirooka H, Nadler JL, Obrosova IG (2012) Interplay of sorbitol pathway of glucose metabolism, 12/15-lipoxygenase, and mitogen-activated protein kinases in the pathogenesis of diabetic peripheral neuropathy. Biochem Pharmacol 83(7):932–940

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  126. Hotta N, Yasuda K, Sumita Y, Sano T, Kakuta H, Nagashima M, Hayashi Y, Yamamoto M, Wakao T, Okuyama M, Kobayashi M, Mori K (2004) Effects of a novel aldose reductase inhibitor, Fidarestat (SNK-860), on vibration perception threshold and subjective symptoms in patients with diabetic polyneuropathy : an open-label pilot study. Clin Drug Investig 24(11):671–680

    Article  CAS  PubMed  Google Scholar 

  127. Bril V, Hirose T, Tomioka S, Buchanan R, Ranirestat Study Group (2009) Ranirestat for the management of diabetic sensorimotor polyneuropathy. Diabetes Care 32(7):1256–1260

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  128. Bril V, Tomioka S, Buchanan RA, Perkins BA (2009) m TSG. Reliability and validity of the modified Toronto clinical neuropathy score in diabetic sensorimotor polyneuropathy. Diabet Med J Br Diabetic Assoc 26(3):240–246

    Article  CAS  Google Scholar 

  129. Ewing DJ, Campbell IW, Clarke BF (1976) Mortality in diabetic autonomic neuropathy. Lancet 1(7960):601–603

    Article  CAS  PubMed  Google Scholar 

  130. Greene DA, Lattimer S, Ulbrecht J, Carroll P (1985) Glucose-induced alterations in nerve metabolism: current perspective on the pathogenesis of diabetic neuropathy and future directions for research and therapy. Diabetes Care 8(3):290–299

    Article  CAS  PubMed  Google Scholar 

  131. Goto Y, Hotta N, Shigeta Y, Sakamoto N, Kikkawa R (1995) Effects of an aldose reductase inhibitor, epalrestat, on diabetic neuropathy. Clinical benefit and indication for the drug assessed from the results of a placebo-controlled double-blind study. Biomed Pharmacother Biomed Pharmacotherapie 49(6):269–277

    Article  CAS  Google Scholar 

  132. Hotta N, Akanuma Y, Kawamori R, Matsuoka K, Oka Y, Shichiri M, Toyota T, Nakashima M, Yoshimura I, Sakamoto N, Shigeta Y (2006) Long-term clinical effects of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy: the 3-year, multicenter, comparative aldose reductase inhibitor-diabetes complications trial. Diabetes Care 29(7):1538–1544

    Article  CAS  PubMed  Google Scholar 

  133. Ikeda T, Iwata K, Tanaka Y (1999) Long-term effect of epalrestat on cardiac autonomic neuropathy in subjects with non-insulin dependent diabetes mellitus. Diabetes Res Clin Pract 43(3):193–198

    Article  CAS  PubMed  Google Scholar 

  134. Sundkvist G, Armstrong FM, Bradbury JE, Chaplin C, Ellis SH, Owens DR, Rosen I, Sonksen P (1992) Peripheral and autonomic nerve function in 259 diabetic patients with peripheral neuropathy treated with ponalrestat (an aldose reductase inhibitor) or placebo for 18 months. United Kingdom/Scandinavian Ponalrestat trial. J Diabetes Complicat 6(2):123–130

    Article  CAS  Google Scholar 

  135. Ziegler D, Mayer P, Rathmann W, Gries FA (1991) One-year treatment with the aldose reductase inhibitor, ponalrestat, in diabetic neuropathy. Diabetes Res Clin Pract 14(1):63–73

    Article  CAS  PubMed  Google Scholar 

  136. Gill JS, Williams G, Ghatei MA, Hetreed AH, Mather HM, Bloom SR (1990) Effect of the aldose reductase inhibitor, ponalrestat, on diabetic neuropathy. Diabete Metab 16(4):296–302

    CAS  PubMed  Google Scholar 

  137. Giugliano D, Marfella R, Quatraro A, De Rosa N, Salvatore T, Cozzolino D, Ceriello A, Torella R (1993) Tolrestat for mild diabetic neuropathy. A 52-week, randomized, placebo-controlled trial. Ann Intern Med 118(1):7–11

    Article  CAS  PubMed  Google Scholar 

  138. Giugliano D, Acampora R, Marfella R, Di Maro G, De Rosa N, Misso L, Ceriello A, Quatraro A, D'Onofrio F (1995) Tolrestat in the primary prevention of diabetic neuropathy. Diabetes Care 18(4):536–541

    Article  CAS  PubMed  Google Scholar 

  139. Kline RC, Swanson DP, Wieland DM, Thrall JH, Gross MD, Pitt B, Beierwaltes WH (1981) Myocardial imaging in man with I-123 meta-iodobenzylguanidine. J Nucl Med Off Publ Soc Nucl Med 22(2):129–132

    CAS  Google Scholar 

  140. Oates PJ (2008) Aldose reductase, still a compelling target for diabetic neuropathy. Curr Drug Targets 9(1):14–36

    Article  CAS  PubMed  Google Scholar 

  141. Pato E, Munoz-Fernandez S, Francisco F, Abad MA, Maese J, Ortiz A, Carmona L, Uveitis Working Group from Spanish Society of Rheumatology (2011) Systematic review on the effectiveness of immunosuppressants and biological therapies in the treatment of autoimmune posterior uveitis. Semin Arthritis Rheum 40(4):314–323

    Article  CAS  PubMed  Google Scholar 

  142. El-Remessy AB, Tang Y, Zhu G, Matragoon S, Khalifa Y, Liu EK, Liu JY, Hanson E, Mian S, Fatteh N, Liou GI (2008) Neuroprotective effects of cannabidiol in endotoxin-induced uveitis: critical role of p38 MAPK activation. Mol Vis 14:2190–2203

    CAS  PubMed Central  PubMed  Google Scholar 

  143. Kalariya NM, Shoeb M, Reddy AB, Sawhney R, Ramana KV (2013) Piceatannol suppresses endotoxin-induced ocular inflammation in rats. Int Immunopharmacol 17(2):439–446

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  144. Rao NA, Kimoto T, Zamir E, Giri R, Wang R, Ito S, Pararajasegaram G, Read RW, Wu GS (2003) Pathogenic role of retinal microglia in experimental uveoretinitis. Invest Ophthalmol Vis Sci 44(1):22–31

    Article  PubMed  Google Scholar 

  145. Coorey NJ, Shen W, Chung SH, Zhu L, Gillies MC (2012) The role of glia in retinal vascular disease. Clin Exp Optom J Aust Optom Assoc 95(3):266–281

    Article  Google Scholar 

  146. Karlstetter M, Ebert S, Langmann T (2010) Microglia in the healthy and degenerating retina: insights from novel mouse models. Immunobiology 215(9–10):685–691

    Article  CAS  PubMed  Google Scholar 

  147. Bousquet E, Zhao M, Ly A, Leroux Les Jardins G, Goldenberg B, Naud MC, Jonet L, Besson-Lescure B, Jaisser F, Farman N, De Kozak Y, Behar-Cohen F (2012) The aldosterone-mineralocorticoid receptor pathway exerts anti-inflammatory effects in endotoxin-induced uveitis. PloS One 7(11):e49036

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  148. Ma W, Zhao L, Fontainhas AM, Fariss RN, Wong WT (2009) Microglia in the mouse retina alter the structure and function of retinal pigmented epithelial cells: a potential cellular interaction relevant to AMD. PLoS One 4(11):e7945

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  149. Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S, Aboyans V, Abraham J, Ackerman I, Aggarwal R, Ahn SY, Ali MK, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Bahalim AN, Barker-Collo S, Barrero LH, Bartels DH, Basanez MG, Baxter A, Bell ML, Benjamin EJ, Bennett D, Bernabe E, Bhalla K, Bhandari B, Bikbov B, Bin Abdulhak A, Birbeck G, Black JA, Blencowe H, Blore JD, Blyth F, Bolliger I, Bonaventure A, Boufous S, Bourne R, Boussinesq M, Braithwaite T, Brayne C, Bridgett L, Brooker S, Brooks P, Brugha TS, Bryan-Hancock C, Bucello C, Buchbinder R, Buckle G, Budke CM, Burch M, Burney P, Burstein R, Calabria B, Campbell B, Canter CE, Carabin H, Carapetis J, Carmona L, Cella C, Charlson F, Chen H, Cheng AT, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahiya M, Dahodwala N, Damsere-Derry J, Danaei G, Davis A, De Leo D, Degenhardt L, Dellavalle R, Delossantos A, Denenberg J, Derrett S, Des Jarlais DC, Dharmaratne SD, Dherani M, Diaz-Torne C, Dolk H, Dorsey ER, Driscoll T, Duber H, Ebel B, Edmond K, Elbaz A, Ali SE, Erskine H, Erwin PJ, Espindola P, Ewoigbokhan SE, Farzadfar F, Feigin V, Felson DT, Ferrari A, Ferri CP, Fevre EM, Finucane MM, Flaxman S, Flood L, Foreman K, Forouzanfar MH, Fowkes FG, Franklin R, Fransen M, Freeman MK, Gabbe BJ, Gabriel SE, Gakidou E, Ganatra HA, Garcia B, Gaspari F, Gillum RF, Gmel G, Gosselin R, Grainger R, Groeger J, Guillemin F, Gunnell D, Gupta R, Haagsma J, Hagan H, Halasa YA, Hall W, Haring D, Haro JM, Harrison JE, Havmoeller R, Hay RJ, Higashi H, Hill C, Hoen B, Hoffman H, Hotez PJ, Hoy D, Huang JJ, Ibeanusi SE, Jacobsen KH, James SL, Jarvis D, Jasrasaria R, Jayaraman S, Johns N, Jonas JB, Karthikeyan G, Kassebaum N, Kawakami N, Keren A, Khoo JP, King CH, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lalloo R, Laslett LL, Lathlean T, Leasher JL, Lee YY, Leigh J, Lim SS, Limb E, Lin JK, Lipnick M, Lipshultz SE, Liu W, Loane M, Ohno SL, Lyons R, Ma J, Mabweijano J, MacIntyre MF, Malekzadeh R, Mallinger L, Manivannan S, Marcenes W, March L, Margolis DJ, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGill N, McGrath J, Medina-Mora ME, Meltzer M, Mensah GA, Merriman TR, Meyer AC, Miglioli V, Miller M, Miller TR, Mitchell PB, Mocumbi AO, Moffitt TE, Mokdad AA, Monasta L, Montico M, Moradi-Lakeh M, Moran A, Morawska L, Mori R, Murdoch ME, Mwaniki MK, Naidoo K, Nair MN, Naldi L, Narayan KM, Nelson PK, Nelson RG, Nevitt MC, Newton CR, Nolte S, Norman P, Norman R, O'Donnell M, O'Hanlon S, Olives C, Omer SB, Ortblad K, Osborne R, Ozgediz D, Page A, Pahari B, Pandian JD, Rivero AP, Patten SB, Pearce N, Padilla RP, Perez-Ruiz F, Perico N, Pesudovs K, Phillips D, Phillips MR, Pierce K, Pion S, Polanczyk GV, Polinder S, Pope CA 3rd, Popova S, Porrini E, Pourmalek F, Prince M, Pullan RL, Ramaiah KD, Ranganathan D, Razavi H, Regan M, Rehm JT, Rein DB, Remuzzi G, Richardson K, Rivara FP, Roberts T, Robinson C, De Leon FR, Ronfani L, Room R, Rosenfeld LC, Rushton L, Sacco RL, Saha S, Sampson U, Sanchez-Riera L, Sanman E, Schwebel DC, Scott JG, Segui-Gomez M, Shahraz S, Shepard DS, Shin H, Shivakoti R, Singh D, Singh GM, Singh JA, Singleton J, Sleet DA, Sliwa K, Smith E, Smith JL, Stapelberg NJ, Steer A, Steiner T, Stolk WA, Stovner LJ, Sudfeld C, Syed S, Tamburlini G, Tavakkoli M, Taylor HR, Taylor JA, Taylor WJ, Thomas B, Thomson WM, Thurston GD, Tleyjeh IM, Tonelli M, Towbin JA, Truelsen T, Tsilimbaris MK, Ubeda C, Undurraga EA, van der Werf MJ, van Os J, Vavilala MS, Venketasubramanian N, Wang M, Wang W, Watt K, Weatherall DJ, Weinstock MA, Weintraub R, Weisskopf MG, Weissman MM, White RA, Whiteford H, Wiersma ST, Wilkinson JD, Williams HC, Williams SR, Witt E, Wolfe F, Woolf AD, Wulf S, Yeh PH, Zaidi AK, Zheng ZJ, Zonies D, Lopez AD, Murray CJ, AlMazroa MA, Memish ZA (2012) Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the global burden of disease study 2010. Lancet 380(9859):2163–2196

    Article  PubMed  PubMed Central  Google Scholar 

  150. Webber S (2011) Diabetes Atlas, 5th edn. Internal Diabetes Federation, Brussels

    Google Scholar 

  151. Klein BE, Klein R, Wang Q, Moss SE (1995) Older-onset diabetes and lens opacities. The beaver dam eye study. Ophthalmic Epidemiol 2(1):49–55

    Article  CAS  PubMed  Google Scholar 

  152. Rowe NG, Mitchell PG, Cumming RG, Wans JJ (2000) Diabetes, fasting blood glucose and age-related cataract: the Blue Mountains eye study. Ophthalmic Epidemiol 7(2):103–114

    Article  CAS  PubMed  Google Scholar 

  153. Leske MC, Wu SY, Hennis A, Connell AM, Hyman L, Schachat A (1999) Diabetes, hypertension, and central obesity as cataract risk factors in a black population. The Barbados eye study. Ophthalmology 106(1):35–41

    Article  CAS  PubMed  Google Scholar 

  154. UK Prospective Diabetes Study (UKPDS) Group (1998) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352(9131):837–853

    Article  Google Scholar 

  155. Spector A (2000) Review: oxidative stress and disease. J Ocul Pharmacol Ther Off J Assoc Ocul Pharmacol Ther 16(2):193–201

    Article  CAS  Google Scholar 

  156. Kyselova Z, Stefek M, Bauer V (2004) Pharmacological prevention of diabetic cataract. J Diabetes Complicat 18(2):129–140

    Article  CAS  Google Scholar 

  157. Mares JA (2004) High-dose antioxidant supplementation and cataract risk. Nutr Rev 62(1):28–32

    Article  PubMed  Google Scholar 

  158. Kador PF (1988) The role of aldose reductase in the development of diabetic complications. Med Res Rev 8(3):325–352

    Article  CAS  PubMed  Google Scholar 

  159. Lee AY, Chung SK, Chung SS (1995) Demonstration that polyol accumulation is responsible for diabetic cataract by the use of transgenic mice expressing the aldose reductase gene in the lens. Proc Natl Acad Sci U S A 92(7):2780–2784

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  160. Snow A, Shieh B, Chang KC, Pal A, Lenhart P, Ammar D, Ruzycki P, Palla S, Reddy GB, Petrash JM (2015) Aldose reductase expression as a risk factor for cataract. Chem Biol Interact 234:247–253

    Article  CAS  PubMed  Google Scholar 

  161. Chan AW, Ho YS, Chung SK, Chung SS (2008) Synergistic effect of osmotic and oxidative stress in slow-developing cataract formation. Exp Eye Res 87(5):454–461

    Article  CAS  PubMed  Google Scholar 

  162. Elwyn H (1946) Diabetic retinopathy. Am J Ophthalmol 29:591

    CAS  PubMed  Google Scholar 

  163. Antonetti DA, Klein R, Gardner TW (2012) Diabetic retinopathy. N Engl J Med 366(13):1227–1239

    Article  CAS  PubMed  Google Scholar 

  164. Campochiaro PA (2013) Ocular neovascularization. J Mol Med 91(3):311–321

    Article  CAS  PubMed  Google Scholar 

  165. Costa PZ, Soares R (2013) Neovascularization in diabetes and its complications. Unraveling the angiogenic paradox. Life Sci 92(22):1037–1045

    Article  CAS  PubMed  Google Scholar 

  166. Tilton RG, Kawamura T, Chang KC, Ido Y, Bjercke RJ, Stephan CC, Brock TA, Williamson JR (1997) Vascular dysfunction induced by elevated glucose levels in rats is mediated by vascular endothelial growth factor. J Clin Invest 99(9):2192–2202

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  167. Nguyen QD, Shah SM, Khwaja AA, Channa R, Hatef E, Do DV, Boyer D, Heier JS, Abraham P, Thach AB, Lit ES, Foster BS, Kruger E, Dugel P, Chang T, Das A, Ciulla TA, Pollack JS, Lim JI, Eliott D, Campochiaro PA, Group R-S (2010) Two-year outcomes of the ranibizumab for edema of the mAcula in diabetes (READ-2) study. Ophthalmology 117(11):2146–2151

    Article  PubMed  Google Scholar 

  168. Michaelides M, Kaines A, Hamilton RD, Fraser-Bell S, Rajendram R, Quhill F, Boos CJ, Xing W, Egan C, Peto T, Bunce C, Leslie RD, Hykin PG (2010) A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2. Ophthalmology 117(6):1078–1086 e2

    Article  PubMed  Google Scholar 

  169. Nishijima K, Ng YS, Zhong L, Bradley J, Schubert W, Jo N, Akita J, Samuelsson SJ, Robinson GS, Adamis AP, Shima DT (2007) Vascular endothelial growth factor-A is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury. Am J Pathol 171(1):53–67

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  170. Bai Y, Ma JX, Guo J, Wang J, Zhu M, Chen Y, Le YZ (2009) Muller cell-derived VEGF is a significant contributor to retinal neovascularization. J Pathol 219(4):446–454

    Article  CAS  PubMed  Google Scholar 

  171. Wang J, Xu X, Elliott MH, Zhu M, Le YZ (2010) Muller cell-derived VEGF is essential for diabetes-induced retinal inflammation and vascular leakage. Diabetes 59(9):2297–2305

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  172. Clements RS Jr, Robison WG Jr, Cohen MP (1998) Anti-glycated albumin therapy ameliorates early retinal microvascular pathology in db/db mice. J Diabetes Complicat 12(1):28–33

    Article  Google Scholar 

  173. Midena E, Segato T, Radin S, di Giorgio G, Meneghini F, Piermarocchi S, Belloni AS (1989) Studies on the retina of the diabetic db/db mouse. I. Endothelial cell-pericyte ratio. Ophthalmic Res 21(2):106–111

    Article  CAS  PubMed  Google Scholar 

  174. Tadayoni R, Paques M, Gaudric A, Vicaut E (2003) Erythrocyte and leukocyte dynamics in the retinal capillaries of diabetic mice. Exp Eye Res 77(4):497–504

    Article  CAS  PubMed  Google Scholar 

  175. Cheung AK, Fung MK, Lo AC, Lam TT, So KF, Chung SS, Chung SK (2005) Aldose reductase deficiency prevents diabetes-induced blood-retinal barrier breakdown, apoptosis, and glial reactivation in the retina of db/db mice. Diabetes 54(11):3119–3125

    Article  CAS  PubMed  Google Scholar 

  176. Grover D, Li TJ, Chong CC (2008) Intravitreal steroids for macular edema in diabetes. Cochrane Database Syst Rev 1:CD005656

    Google Scholar 

  177. Payne AS, Freishtat RJ (2012) Conserved steroid hormone homology converges on nuclear factor kappaB to modulate inflammation in asthma. J Invest Med Off Publ Am Fed Clin Res 60(1):13–17

    CAS  Google Scholar 

  178. Cechin SR, Buchwald P (2014) Effects of representative glucocorticoids on TNFalpha- and CD40L-induced NF-kappaB activation in sensor cells. Steroids 85:36–43

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  179. Yumusak E, Buyuktortop N, Ornek K (2015) Early results of dexamethasone implant, ranibizumab, and triamcinolone in macular edema due to branch retinal vein occlusion. Eur J Ophthalmol 26:54–59

    Article  PubMed  Google Scholar 

  180. Hotamisligil GS (2006) Inflammation and metabolic disorders. Nature 444(7121):860–867

    Article  CAS  PubMed  Google Scholar 

  181. 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 (London, England) 20(12):1366–1369

    Article  CAS  Google Scholar 

  182. Aveleira CA, Lin CM, Abcouwer SF, Ambrosio AF, Antonetti DA (2010) TNF-alpha signals through PKCzeta/NF-kappaB to alter the tight junction complex and increase retinal endothelial cell permeability. Diabetes 59(11):2872–2882

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  183. Krady JK, Basu A, Allen CM, Xu Y, LaNoue KF, Gardner TW, Levison SW (2005) Minocycline reduces proinflammatory cytokine expression, microglial activation, and caspase-3 activation in a rodent model of diabetic retinopathy. Diabetes 54(5):1559–1565

    Article  CAS  PubMed  Google Scholar 

  184. Diabetic Retinopathy Clinical Research Network, Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR, Ferris FL 3rd, Friedman SM, Glassman AR, Miller KM, Scott IU, Stockdale CR, Sun JK (2010) Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 117(6):1064–1077 e35

    Article  Google Scholar 

  185. Navaratna D, McGuire PG, Menicucci G, Das A (2007) Proteolytic degradation of VE-cadherin alters the blood-retinal barrier in diabetes. Diabetes 56(9):2380–2387

    Article  CAS  PubMed  Google Scholar 

  186. Sabbatini M, Sansone G, Uccello F, Giliberti A, Conte G, Andreucci VE (1992) Early glycosylation products induce glomerular hyperfiltration in normal rats. Kidney Int 42(4):875–881

    Article  CAS  PubMed  Google Scholar 

  187. Stitt AW (2010) AGEs and diabetic retinopathy. Invest Ophthalmol Vis Sci 51(10):4867–4874

    Article  PubMed  Google Scholar 

  188. Ibrahim AS, El-Remessy AB, Matragoon S, Zhang W, Patel Y, Khan S, Al-Gayyar MM, El-Shishtawy MM, Liou GI (2011) Retinal microglial activation and inflammation induced by amadori-glycated albumin in a rat model of diabetes. Diabetes 60(4):1122–1133

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  189. Heidland A, Sebekova K, Schinzel R (2001) Advanced glycation end products and the progressive course of renal disease. Am J Kidney Dis Off J Natil Kidney Found 38(4 Suppl 1):S100–S106

    Article  CAS  Google Scholar 

  190. Dong N, Chang L, Wang B, Chu L (2014) Retinal neuronal MCP-1 induced by AGEs stimulates TNF-alpha expression in rat microglia via p38, ERK, and NF-kappaB pathways. Mol Vis 20:616–628

    PubMed Central  PubMed  Google Scholar 

  191. Wang AL, Yu AC, He QH, Zhu X, Tso MO (2007) AGEs mediated expression and secretion of TNF alpha in rat retinal microglia. Exp Eye Res 84(5):905–913

    Article  CAS  PubMed  Google Scholar 

  192. Dewey S (2006) Posterior capsule opacification. Curr Opin Ophthalmol 17(1):45–53

    Article  PubMed  Google Scholar 

  193. Wormstone IM (2002) Posterior capsule opacification: a cell biological perspective. Exp Eye Res 74(3):337–347

    Article  CAS  PubMed  Google Scholar 

  194. Wormstone IM, Tamiya S, Anderson I, Duncan G (2002) TGF-beta2-induced matrix modification and cell transdifferentiation in the human lens capsular bag. Invest Ophthalmol Vis Sci 43(7):2301–2308

    PubMed  Google Scholar 

  195. Hales AM, Schulz MW, Chamberlain CG, McAvoy JW (1994) TGF-beta 1 induces lens cells to accumulate alpha-smooth muscle actin, a marker for subcapsular cataracts. Curr Eye Res 13(12):885–890

    Article  CAS  PubMed  Google Scholar 

  196. Pladzyk A, Reddy AB, Yadav UC, Tammali R, Ramana KV, Srivastava SK (2006) Inhibition of aldose reductase prevents lipopolysaccharide-induced inflammatory response in human lens epithelial cells. Invest Ophthalmol Vis Sci 47(12):5395–5403

    Article  PubMed  Google Scholar 

  197. Reddy AB, Ramana KV, Srivastava S, Bhatnagar A, Srivastava SK (2009) Aldose reductase regulates high glucose-induced ectodomain shedding of tumor necrosis factor (TNF)-alpha via protein kinase C-delta and TNF-alpha converting enzyme in vascular smooth muscle cells. Endocrinology 150(1):63–74

    Article  CAS  PubMed  Google Scholar 

  198. Yoon J, Lee H, Chang HB, Choi H, Kim YS, Rho YK, Seong S, Choi DH, Park D, Ku B (2014) DW1029M, a novel botanical drug candidate, inhibits advanced glycation end-product formation, rat lens aldose reductase activity, and TGF-beta1 signaling. Am J Physiol Renal Physiol 306(10):F1161–F1170

    Article  CAS  PubMed  Google Scholar 

  199. Yadav UC, Ighani-Hosseinabad F, van Kuijk FJ, Srivastava SK, Ramana KV (2009) Prevention of posterior capsular opacification through aldose reductase inhibition. Invest Ophthalmol Vis Sci 50(2):752–759

    Article  PubMed  Google Scholar 

  200. Shi Y, Massague J (2003) Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 113(6):685–700

    Article  CAS  PubMed  Google Scholar 

  201. Derynck R, Akhurst RJ, Balmain A (2001) TGF-beta signaling in tumor suppression and cancer progression. Nat Genet 29(2):117–129

    Article  CAS  PubMed  Google Scholar 

  202. Chang KC, Petrash JM (2015) Aldose reductase mediates transforming growth factor beta2 (TGF-beta2)-induced migration and epithelial-to-mesenchymal transition of lens-derived epithelial cells. Invest Ophthalmol Vis Sci 56(8):4198–4210

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  203. Li L, Chang KC, Zhou Y, Shieh B, Ponder J, Abraham AD, Ali H, Snow A, Petrash JM, LaBarbera DV (2014) Design of an amide N-glycoside derivative of beta-glucogallin: a stable, potent, and specific inhibitor of aldose reductase. J Med Chem 57(1):71–77

    Article  CAS  PubMed  Google Scholar 

  204. Riley RJ, Maggs JL, Lambert C, Kitteringham NR, Park BK (1988) An in vitro study of the microsomal metabolism and cellular toxicity of phenytoin, sorbinil and mianserin. Br J Clin Pharmacol 26(5):577–588

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  205. Suzen S, Buyukbingol E (2003) Recent studies of aldose reductase enzyme inhibition for diabetic complications. Curr Med Chem 10(15):1329–1352

    Article  CAS  PubMed  Google Scholar 

  206. Chalk C, Benstead TJ, Moore F (2007) Aldose reductase inhibitors for the treatment of diabetic polyneuropathy. Cochrane Database Syst Rev 4:CD004572

    Google Scholar 

  207. Gabbay KH (2004) Aldose reductase inhibition in the treatment of diabetic neuropathy: where are we in 2004? Curr Diab Rep 4(6):405–408

    Article  PubMed  Google Scholar 

  208. Ludvigson MA, Sorenson RL (1980) Immunohistochemical localization of aldose reductase.II Rat eye and kidney. Diabetes 29(6):450–459

    Article  CAS  PubMed  Google Scholar 

  209. Chakrabarti S, Sima AA, Nakajima T, Yagihashi S, Greene DA (1987) Aldose reductase in the BB rat: isolation, immunological identification and localization in the retina and peripheral nerve. Diabetologia 30(4):244–251

    Article  CAS  PubMed  Google Scholar 

  210. Guidry C (2005) The role of Muller cells in fibrocontractive retinal disorders. Prog Retin Eye Res 24(1):75–86

    Article  CAS  PubMed  Google Scholar 

  211. Wang JJ, Zhu M, Le YZ (2015) Functions of Muller cell-derived vascular endothelial growth factor in diabetic retinopathy. World J Diabetes 6(5):726–733

    Article  PubMed Central  PubMed  Google Scholar 

  212. Verwaerde C, Naud MC, Delanoye A, Wood M, Thillaye-Goldenberg B, Auriault C, de Kozak Y (2003) Ocular transfer of retinal glial cells transduced ex vivo with adenovirus expressing viral IL-10 or CTLA4-Ig inhibits experimental autoimmune uveoretinitis. Gene Ther 10(23):1970–1981

    Article  CAS  PubMed  Google Scholar 

  213. Anker SD, von Haehling S (2004) Inflammatory mediators in chronic heart failure: an overview. Heart 90(4):464–470

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  214. Madge LA, Pober JS (2001) TNF signaling in vascular endothelial cells. Exp Mol Pathol 70(3):317–325

    Article  CAS  PubMed  Google Scholar 

  215. Ramana KV, Bhatnagar A, Srivastava SK (2004) Inhibition of aldose reductase attenuates TNF-alpha-induced expression of adhesion molecules in endothelial cells. FASEB J : Off Publ Fed Am Soc Exp Biol 18(11):1209–1218

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Ophthalmology, School of Medicine, University of Colorado, Aurora, CO, USA

    Kun-Che Chang & J. Mark Petrash

  2. Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA

    Kun-Che Chang & J. Mark Petrash

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  1. Kun-Che Chang
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  2. J. Mark Petrash
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Correspondence to J. Mark Petrash .

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Editors and Affiliations

  1. Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, USA

    Vasilis Vasiliou

  2. Distilled Spirits Council of the US, Washington, DC, USA

    Samir Zakhari

  3. Mishra Laboratory, University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    Lopa Mishra

  4. Salem Medical Centre, University of Heidelberg, Heidelberg, Baden-Württemberg, Germany

    Helmut K. Seitz

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Chang, KC., Petrash, J.M. (2018). Aldo-Keto Reductases: Multifunctional Proteins as Therapeutic Targets in Diabetes and Inflammatory Disease. In: Vasiliou, V., Zakhari, S., Mishra, L., Seitz, H. (eds) Alcohol and Cancer. Advances in Experimental Medicine and Biology, vol 1032. Springer, Cham. https://doi.org/10.1007/978-3-319-98788-0_13

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