Aldose Reductase and Complications of the Eye

  • Margo Panush Cohen

Abstract

The paradigm for the participation of the polyol pathway in the pathogenesis of a complication of diabetes is the ocular lens, the first tissue in which an association between excess sorbitol formation and a pathologic change was described. The discovery by Von Heyningen that the lenses of rats in which cataracts had been induced by diabetes, or by galactose or xylose feeding, contained increased amounts of the respective sugar alcohols sorbitol, galactitol, and xylitol provided an explanation for certain histopathologic features that had been observed in developing cataracts.1,2 These features consisted of the early appearance of hydropic lens fibers, followed by rupture of the swollen fibers, liquefaction, and replacement by vacuoles or interfibrillar clefts.

Keywords

Xylose NADPH Quercetin Indomethacin Fluorescein 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Van Heyningen R: Formation of polyols by the lens of the rat with sugar cataracts. Nature (Lond) 1959; 184:194–195.CrossRefGoogle Scholar
  2. 2.
    Van Heyningen R: Metabolism of xylose by the lens. Rat lens in vivo and in vitro. Biochem J 1959; 73:197–207.Google Scholar
  3. 3.
    LeFevre PG, Davis R: Active transport into the human erythrocyte: Evidence from comparative kinetics and composition among monosaccharides. J Gen Physiol 1951; 34:515–524.CrossRefGoogle Scholar
  4. 4.
    Wick AN, Drury DR: Insulin and permeability of cells to sorbitol. Am J Physiol 1951; 166:421–423.PubMedGoogle Scholar
  5. 5.
    Kinoshita JH, Merola LO, Satoh K, et al: Osmotic changes caused by the accumulation of dulcitol in the lenses of rats fed with galactose. Nature (Lond) 1962; 194:1085–1087.CrossRefGoogle Scholar
  6. 6.
    Kinoshita JH, Merola LO, Dikmak E: Osmotic changes in experimental galactose cataracts. Exp Eye Res 1962; 1:405–410.PubMedCrossRefGoogle Scholar
  7. 7.
    Kinoshita JH, Merola LO, Dikmak E: The accumulation of dulcitol and water in rabbit lens incubated with galactose. Biochim Biophys Acta 1962; 62:176–178.PubMedCrossRefGoogle Scholar
  8. 8.
    Kinoshita JH, Merola LO: Hydration of the lens during the development of galactose cataract. Invest Ophthalmol 1964; 3:577–584.PubMedGoogle Scholar
  9. 9.
    Kinoshita JH, Futterman S, Satoh K, et al: Factors affecting the formation of sugar alcohols in ocular lens. Biochim Biophys Acta 1963; 74:340–350.PubMedCrossRefGoogle Scholar
  10. 10.
    Kinoshita JH: Cataracts in galactosemia. Invest Ophthalmol 1965; 4:786–799.PubMedGoogle Scholar
  11. 11.
    Kinoshita JH: Mechanisms initating cataract formation. Invest Ophthalmol 1974; 13:713–724.PubMedGoogle Scholar
  12. 12.
    Kinoshita JH, Fukushi S, Kador P, et al: Aldose reductase in diabetic complications of the eye. Metabolism 1979; 28:462–469.PubMedCrossRefGoogle Scholar
  13. 13.
    Kuwabara T, Kinoshita JH, Cogan DC: Electron microscopic study of galactose-induced cataract. Invest Ophthalmol 1969; 8:133–149.PubMedGoogle Scholar
  14. 14.
    Duke-Elder WS: Changes in refraction in diabetes mellitus. Br J Ophthalmol 1925; 9:167–187.PubMedCrossRefGoogle Scholar
  15. 15.
    Vere DW, Verrel D: Relation between blood sugar level and the optical properties of the lens of the human eye. Clin Sci 1955; 14:183–196.Google Scholar
  16. 16.
    Varma SD, El-Aguizy HK, Richards RD: Refractive changes in alloxan diabetic rabbits. Control by flavinoids. Acta Ophthalmol 1980; 58:748–759.Google Scholar
  17. 17.
    Kinoshita JH, Merola LO, Hayman S: Osmotic effects on the amino acid-concentrating mechanism in the rabbit lens. J Biol Chem 1965; 240:313–315.Google Scholar
  18. 18.
    Kinoshita JH, Merola O, Tung B: Changes in cation permeability in the galactose-exposed rabbit lens. Exp Eye Res 1968; 7:80–90.PubMedCrossRefGoogle Scholar
  19. 19.
    Chylack LT Jr, Kinoshita JH: A biochemical evaluation of a cataract induced in a high glucose medium. Invest Ophthalmol 1969: 8:401–412.PubMedGoogle Scholar
  20. 20.
    Varma SD, Kinoshita JH: Sorbitol pathway in diabetic galactosemic rat lens. Biochim Biophys Acta 1974; 338:632–640.Google Scholar
  21. 21.
    Cotlier E: Myoinositol: Active transport by the crystalline lens. Invest Ophthalmol 1970; 9:681–691.PubMedGoogle Scholar
  22. 22.
    Broekhuyse RM: Changes in myo-inositol permeability in the lens due to cataractous conditions. Biochim Biophys Acta 1968; 163:269–272.PubMedCrossRefGoogle Scholar
  23. 23.
    Sippel TO: Changes in the water, protein and glutathione contents of the lens in the course of galactose cataract development in rats. Invest Ophthalmol 1960; 5:568–575.Google Scholar
  24. 24.
    Kinoshita JH, Barber GW, Merola LD, et al: Changes in the levels of free amino acids and myoinositol in the galactose-exposed lens. Invest Ophthalmol 1969; 8:625–632.PubMedGoogle Scholar
  25. 25.
    Reddy VN, Schauss D, Chakrapani B, et al: Biochemical changes associated with the development and reversal of galactose cataracts. Exp Eye Res 1976; 23:483–493.PubMedCrossRefGoogle Scholar
  26. 26.
    Kador PF, Zigler S, Kinoshita JH: Alterations of lens protein synthesis in galactosemic rats. Invest Ophthalmol Vis Sci 1979; 18:696–702.PubMedGoogle Scholar
  27. 27.
    Lee SM, Schade SZ, Doughty CC: Aldose reductase, NADPH and NADP+ in normal, galactose-fed and diabetic rat lens. Biochim Biophys Acta 1985; 841:247–253.PubMedGoogle Scholar
  28. 28.
    Unakar NJ, Tsui JY: Inhibition of galactose-induced alterations in ocular lens with Sorbinil. Exp Eye Res 1983; 36:685–694.PubMedCrossRefGoogle Scholar
  29. 29.
    Gonzalez AM, Sochor M, McLean P: Effect of experimental diabetes on glycolytic intermediates and regulation of phosphofructokinase in rat lens. Biochem Biophys Res Commun 1980; 95:1173–1179.PubMedCrossRefGoogle Scholar
  30. 30.
    Gonzalez AM, Sochor M, Rowles PM, et al: Sequential biochemical and structural changes occurring in rat lens during cataract formation in experimental diabetes. Diabetologia 1981; 21:5.Google Scholar
  31. 31.
    Gonzalez AM, Sochor M, McLean P: The effect of an aldose reductase inhibitor (Sorbinil) on the level of metabolites in lenses of diabetic rats. Diabetes 1983; 32:482–485.PubMedCrossRefGoogle Scholar
  32. 32.
    Bhuyan KC, Bhuyan DK, Katzin DM: Amizol-induced cataract and inhibition of lens catalase in rabbit. Ophthalmic Res 1973; 5:236–247.CrossRefGoogle Scholar
  33. 33.
    Reddy VN: Metabolism of glutathione in the lens. Exp Eye Res 1971; 11:310–328.PubMedCrossRefGoogle Scholar
  34. 34.
    Varma SD, Kumar S, Richards RD: Protection by ascorbate against superoxide injury to the lens. Invest Ophthalmol Vis Sci 1979; 18(suppl):98.Google Scholar
  35. 35.
    Varma SD: Superoxide and lens of the eye. A new theory of cataractogenesis. Int J Quantum Chem 1981; 20:479–484.CrossRefGoogle Scholar
  36. 36.
    Goosey JD, Zigler JS Jr, Kinoshita JH: Cross-linking of lens crystallins in a photodynamic system. A singlet oxygen mediated process. Science 1980; 208:1278–1279.PubMedCrossRefGoogle Scholar
  37. 37.
    Dische Z, Zil H: Studies on the oxidation of cysteine to cystine in lens protein during cataract formation. Am J Ophthalmol 1951; 34:104–113.PubMedGoogle Scholar
  38. 38.
    Garner MH, Spector A: Selective oxidation of cysteine and methionine in normal and cataractous lens. Proc Natl Acad Sci USA 1980; 77:1274–1277.PubMedCrossRefGoogle Scholar
  39. 39.
    Creighton MO, Trevithick JR: Cortical cataract formation prevented by vitamin E and glutathione. Exp Eye Res 1979; 29:689–693.PubMedCrossRefGoogle Scholar
  40. 40.
    Ross WM, Creighton MO, Stewart-DeHaan PJ, et al: Modelling cortical cataractogenesis: 3. In vivo effects of vitamin E on cataractogenesis in diabetic rats. Can J Ophthalmol 1982; 17:61–66.PubMedGoogle Scholar
  41. 41.
    Chand D, El-Aguizy K, Richards RD, et al: Sugar cataracts in vitro: Implications of oxidative stress and aldose reductase I. Exp Eye Res 1982; 35:491–497.PubMedCrossRefGoogle Scholar
  42. 42.
    Kadoya K, Hashi H, Yui MNH, et al: Influences of aldose reductase inhibitor on peroxidation reaction in the lens of streptozotocin diabetic rats. Nippon Ganka Kiyo 1983; 34:2172–2176.Google Scholar
  43. 43.
    Cogan DG, Kinoshita KH, Kador PF, et al: Aldose reductase and complications of diabetes. Ann Intern Med 1984; 101:82–91.PubMedGoogle Scholar
  44. 44.
    Gabbay KH: The sorbitol pathway and complications of diabetes. N Engl J Med 1973; 288:831–836.PubMedCrossRefGoogle Scholar
  45. 45.
    Varma SD, Kinoshita JH: The absence of cataracts in mice with congenital hyperglycemia. Exp Eye Res 1974; 19:577–582.PubMedCrossRefGoogle Scholar
  46. 46.
    Varma SD, Mikuni I, Kinoshita JH: Flavinoids as inhibitors of lens aldose reductase. Science 1975; 188:1215–1216.PubMedCrossRefGoogle Scholar
  47. 47.
    El-Aguizy HK, Richards RD, Varma SD: Sugar cataracts in mongolian gerbil (Meriones unguiculatus). Exp Eye Res 1983; 36:839–844.PubMedCrossRefGoogle Scholar
  48. 48.
    Obazawa H, Merola LO, Kinoshita JH: The effects of xylose on the isolated lens. Invest Ophthalmol 1974; 13:204–209.PubMedGoogle Scholar
  49. 49.
    Kinoshita JH, Dvornik D, Kraml M, et al: The effect of an aldose reductase inhibitor on the galactose-exposed rabbit lens. Biochim Biophys Acta 1968; 158:472–475.PubMedGoogle Scholar
  50. 50.
    Dvornik D, Simard-Duquesne N, Kraml M, et al: Polyol accumulation in galactosemic and diabetic rats: Control by an aldose reductase inhibitor. Science 1973; 182:1146–1148.PubMedCrossRefGoogle Scholar
  51. 51.
    Chylack LT Jr, Henriques HF, Cheng H-M, et al: Efficacy of alrestatin, an aldose reductase inhibitor, in human diabetic and nondiabetic lenses. Ophthalmology 1979; 86:1579–1585.PubMedGoogle Scholar
  52. 52.
    Simard-Duquesne N, Greslin E, Gonzalez R, et al: Prevention of cataract development in severely galactosemic rats by the aldose reductase inhibitor, tolrestat. Proc Soc Exp Biol Med 1985; 178:599–605.PubMedGoogle Scholar
  53. 53.
    Simard-Duquesne N, Greslin E, Dubuc J, et al: The effect of a new aldose reductase inhibitor (tolrestat) in galactosemic and diabetic rats. Metabolism 1985; 34:885–892.PubMedCrossRefGoogle Scholar
  54. 54.
    Peterson MJ, Sarges R, Aldinger CE, et al: CP-45,634: A novel aldose reductase inhibitor that inhibits polyol pathway activity in diabetic and galactosemic rats. Metabolism 1979; 28(suppl 1):456–461.PubMedCrossRefGoogle Scholar
  55. 55.
    Beyer-Mears A, Cruz E, Nicolas-Alexandre J, et al: Sorbinil protection of lens protein components and cell hydration during diabetic cataract formation. Pharmacology 1982; 24:193–200.PubMedCrossRefGoogle Scholar
  56. 56.
    Datiles M, Fukui H, Kuwabara T, et al: Galactose cataract prevention with Sorbinil, an aldose reductase inhibitor: A light microscopic study. Invest Ophthalmol Vis Sci 1982; 22:174–179.PubMedGoogle Scholar
  57. 57.
    Peterson MJ, Sarges R, Aldinger CE, et al: Inhibition of polyol pathway activity in diabetic and galactosemic rats by the aldose reductase inhibitor CP-45,634. Adv Exp Med Biol 1979; 119:347–356.PubMedGoogle Scholar
  58. 58.
    Fukushi H, Merola L, Kinoshita JH: Altering the course of cataracts in diabetic rats. Invest Ophthalmol Vis Sci 1980; 19:313–315.PubMedGoogle Scholar
  59. 59.
    Poulsom R, Boot-Hanford RP, Heath H: Some effects of aldose reductase inhibition upon the eyes of long-term streptozotocin-diabetic rats. Curr Eye Res 1982; 2:351–355.PubMedCrossRefGoogle Scholar
  60. 60.
    Ono H, Nozawa Y, Hayano S: Effects of M-79,175, an aldose reductase inhibitor, on experimental sugar cataracts. Nippon Ganka Gakkai Zasshi 1982; 86:1343–1350.PubMedGoogle Scholar
  61. 61.
    Beyer-Mears A, Farnsworth PN: Diminished diabetic cataractogenesis by quercetin. Exp Eye Res 1979; 28:709–716.PubMedCrossRefGoogle Scholar
  62. 62.
    Varma SD, Mizuno A, Kinoshita JH: Diabetic cataracts and flavinoids. Science 1977; 195:205–206.PubMedCrossRefGoogle Scholar
  63. 63.
    Varma SD, Shockert SS, Richards RD: Implications of aldose reductase in cataracts in human diabetics. Invest Ophthalmol Vis Sei 1979; 18:237–241.Google Scholar
  64. 64.
    Beyer-Mears A, Cruz E, Nicolas-Alexandre J, et al: Xanthone-2-carboxylic acid effect on lens growth, hydration and proteins during diabetic cataract development. Arch Int Pharmacodyn Ther 1982; 259:166–176.PubMedGoogle Scholar
  65. 65.
    Sharma YR, Cotlier E: Inhibition of lens and cataract aldose reductase by protein-bound anti-rheumatic drugs: Salicylate, indomethacin, oxyphenbuta-zone, sulindac. Exp Eye Res 1982; 35:21–27.PubMedCrossRefGoogle Scholar
  66. 66.
    Jacobson M, Sharma YR, Cotlier E, et al: Diabetic complications in lens and nerve and their prevention by sulindac or Sorbinil: Two novel aldose reductase inhibitors. Invest Ophthalmol Vis Sei 1983; 24:1426–1429.Google Scholar
  67. 67.
    Crabbe MJC, Freeman G, Halder G, et al: The inhibition of bovine lens aldose reductase by Clinoril, its absorption into human red cell and its effect on human red cell aldose reductase activity. Ophthalmic Res 1985; 17:85–89.PubMedCrossRefGoogle Scholar
  68. 68.
    Cotlier E, Fagadau W, Cicchetti DV: Methods for evaluation of medical therapy of senile and diabetic cataracts. Trans Ophthalmol Soc UK 1982; 102:416–422.PubMedGoogle Scholar
  69. 69.
    Cotlier E, Sharma YR, Niven T, et al: Distribution of salicylate in lens and intraocular fluids and its effect on cataract formation. Am J Med 1983; 75(6A):83–90.CrossRefGoogle Scholar
  70. 70.
    Hu T-S, Datiles M, Kinoshita JH: Reversal of galactose cataract with sorbinil in rats. Invest Ophthalmol Vis Sei 1983; 24:640–644.Google Scholar
  71. 71.
    Beyer-Mears A, Cruz E: Reversal of diabetic cataract by sorbinil, an aldose reductase inhibitor. Diabetes 1985; 34:15–21.PubMedCrossRefGoogle Scholar
  72. 72.
    Hockwin O, Bergeder HD, Kaiser L: Über die Galaktosekatarakt junger Ratten nach Ganzkorperröntgenbestrahlung. Ber Dtsch Ophthalmol Ges 1967; 68:135–139.Google Scholar
  73. 73.
    Hockwin O, Bergeder HD, Ninnemann U, et al: Untersuchungen zur Latenzzeit der Galaktosekatarakt von Ratten. Einfluss von Röntgenbestrahlung und Diätbeginn bei verschieden alten Tieren. Graefes Arch Klin Opthalmol 1974; 189:171–178.CrossRefGoogle Scholar
  74. 74.
    Keller H-W, Stinnesbeck TH, Hockwin O, et al: Investigations on the influence of whole body X-irradiation on the activity of rat lens aldose reductase (E.C.I. 1.1.21). Graefes Arch Klin Opthalmol 1981; 215:181–186.CrossRefGoogle Scholar
  75. 75.
    Chylack LT Jr, Henriques H, Tung W: Inhibition of sorbitol production in human lenses by an aldose reductase inhibitor. Invest Ophthalmol Vis Sci 1978; 17(ARVO suppl):300.Google Scholar
  76. 76.
    Lerner BC, Varma SD, Richards RD: Polyol pathway metabolites in human cataracts. Arch Ophthalmol 1984; 102:917–920.PubMedGoogle Scholar
  77. 77.
    Jedziniak JA, Chylack LT, Chen H-M, et al: The sorbitol pathway in the human lens: Aldose reductase and polyol dehydrogenase. Invest Ophthalmol Vis Sci 1981; 20:314–326.PubMedGoogle Scholar
  78. 78.
    Davies PD, Duncan G, Pynsent PB, et al: Aqueous humor glucose concentration in cataract patients and its effect on the lens. Exp Eye Res 1984; 39:605–609.PubMedCrossRefGoogle Scholar
  79. 79.
    Reddy DVN, Kinsey VE: Transport of amino acids into intraocular fluids and lens in diabetic rabbits. Invest Ophthalmol 1963; 2:237–242.PubMedGoogle Scholar
  80. 80.
    Reddy DVN: Amino acid transport in the lens in relation to sugar cataracts. Invest Ophthalmol 1965; 4:700–706.PubMedGoogle Scholar
  81. 81.
    Reddy VN, Chakrapani B, Steen D: Sorbitol pathway in the ciliary body in relation to accumulation of amino acids in the aqueous humor of alloxan diabetic rabbits. Invest Ophthalmol 1971; 100:870–875.Google Scholar
  82. 82.
    Cohen MP: Diabetes and Protein Glycosylation: Measurement and Biologic Relevance. New York, Springer-Verlag, 1986.Google Scholar
  83. 83.
    Chiou SH, Chylack LT, Bunn HF, et al: Role of nonenzymatic glycosylation in experimental cataract formation. Biochem Biophys Res Commun 1980; 95:894–901.PubMedCrossRefGoogle Scholar
  84. 84.
    Cotlier E: Aspirin effect on cataract formation in patients with rheumatoid arthritis alone or combined with diabetes. Int Ophthalmol 1981; 3:173–179.PubMedCrossRefGoogle Scholar
  85. 85.
    Bous F, Hockwin O, Ohrloff C, et al: Investigation on phosphofructokinase (EC 2.7.1.11) in bovine lens in dependence on age, topographic distribution and water soluble protein fractions. Exp Eye Res 1977; 24:383–389.PubMedCrossRefGoogle Scholar
  86. 86.
    Chen HM, Chylack LT Jr: Factors affecting the rate of lactate production in rat lens. Ophthalmic Res 1977; 9:381–387.CrossRefGoogle Scholar
  87. 87.
    Ohrloff C, Zierz S, Hockwin O: Investigations of the enzymes involved in the fructose breakdown in the cattle lens. Ophthalmic Res 1982; 14:221–229.PubMedCrossRefGoogle Scholar
  88. 88.
    Siddiqui MA, Rahman MA: Effect of hyperglycemia on the enzyme activities of lenticular tissue of rats. Exp Eye Res 1980; 31:463–469.PubMedCrossRefGoogle Scholar
  89. 89.
    Chylack LT, Cheng H-M: Sugar metabolism in the crystalline lens. Surv Ophthalmol 1978; 23:26–34.PubMedCrossRefGoogle Scholar
  90. 90.
    Hollows JC, Schofield PJ, Williams JF, et al: The effect of an unsaturated fat-diet on cataract formation in streptozotocin-induced diabetic rats. Br J Nutr 1976; 36:161–177.PubMedCrossRefGoogle Scholar
  91. 91.
    Kahn HA, Liebowitz HM, Ganley JP, et al: The Framingham eye study. II. Association of ophthalmic pathology with single variables previously measured in the Framingham study. Am J Epidemiol 1977; 106:33–41.PubMedGoogle Scholar
  92. 92.
    Barnett PA, Gonzalez RG, Chylack LT, et al: The effect of oxidation on sorbitol pathway kinetics. Diabetes 1986; 35:426–432.PubMedCrossRefGoogle Scholar
  93. 93.
    Kuwabara T, Cogan DG: Retinal vascular patterns. VI. Mural cells of the retinal capillaries. Arch Ophthalmol 1963; 69:492–502.PubMedGoogle Scholar
  94. 94.
    Hogan MJ, Feeney L: The ultrastructure of the retinal vessels. II. The small vessels. J Ultrastruct Res 1963; 9:29–46.CrossRefGoogle Scholar
  95. 95.
    Ishikawa T: Fine structure of retinal vessels in man and the macaque monkey. Invest Ophthalmol 1963; 2:1–15.PubMedGoogle Scholar
  96. 96.
    Shakib M, Cunha-Vaz JG: Studies on the permeability of the blood retinal barrier. IV. Junctional complexes of the retinal vessels and their role in the permeability of the blood retinal barrier. Exp Eye Res 1966; 5:229–234.PubMedCrossRefGoogle Scholar
  97. 97.
    Speiser P, Gittelsohn AM, Patz A: Studies on diabetic retinopathy. III. Influence of diabetes on intramural pericytes. Arch Ophthalmol 1968; 80:332–337.PubMedGoogle Scholar
  98. 98.
    Yanoff M: Diabetic retinopathy. N Engl J Med 1966; 274:1344–1349.PubMedCrossRefGoogle Scholar
  99. 99.
    Addison DJ, Garner A, Ashton N: Degeneration of intramural pericytes in diabetic retinopathy. Br Med J 1970; 1:264–266.PubMedCrossRefGoogle Scholar
  100. 100.
    Cogan DG, Toussaint D, Kuwabara T: Retinal vascular patterns. IV. Diabetic retinopathy. Arch Ophthalmol 1976; 66:366–372.Google Scholar
  101. 101.
    Ashton N: The blood-retinal barrier and vaso-glial relationships in retinal disease. Trans Ophthalmol Soc UK 1965; 85:199–230.PubMedGoogle Scholar
  102. 102.
    Cunha-Vaz J, DeAbreau JRF, Campos AJ, et al: Early breakdown of the blood-retinal barrier in diabetes. Br J Ophthalmol 1975; 59:649–656.PubMedCrossRefGoogle Scholar
  103. 103.
    Waltman S, Krupin T, Hanish S, et al: Alteration of the blood retinal barrier in experimental diabetes mellitus. Arch Ophthalmol 1978; 96:878–879.PubMedGoogle Scholar
  104. 104.
    Wise GN, Dollery GT, Henkind P: The Retinal Circulation, pp 290–324, 350–420. New York, Harper & Row, 1971.Google Scholar
  105. 105.
    Gabbay KH: Purification and immunological identification of bovine retinal aldose reductase. Isr J Med Sci 1972; 8:1626–1628.PubMedGoogle Scholar
  106. 106.
    Akagi Y, Kador PF, Kuwabara T, et al: Aldose reductase localization in human retinal mural cells. Invest Ophthalmol Vis Sci 1983; 24:1516–1519.PubMedGoogle Scholar
  107. 107.
    Ludvigson MA, Sorenson RL: Immunohistochemical localization of aldose reductase. II. Rat eye and kidney. Diabetes 1980; 29:450–459.PubMedCrossRefGoogle Scholar
  108. 108.
    Kern TS, Engerman RL: Distribution of aldose reductase in ocular tissues. Exp Eye Res 1981; 33:175–182.PubMedCrossRefGoogle Scholar
  109. 109.
    Akagi Y, Yajima Y, Kador PF, et al: Localization of aldose reductase in the human eye. Diabetes 1984; 33:562–566.PubMedCrossRefGoogle Scholar
  110. 110.
    Buzney SM, Frank RN, Varma SD, et al: Aldose reductase in retinal mural cells. Invest Ophthalmol Vis Sci 1977; 16:392–396.PubMedGoogle Scholar
  111. 111.
    Kern TS, Engerman RL: Hexitol production by canine retinal microvessels. Invest Ophthalmol Vis Sci 1985; 26:382–384.PubMedGoogle Scholar
  112. 112.
    Russell P, Merola LO, Yajima Y, et al: Aldose reductase activity in a cultured human retinal cell line. Exp Eye Res 1982; 35:331–336.PubMedCrossRefGoogle Scholar
  113. 113.
    Li W, Chan LS, Khatami M, et al: Characterization of glucose transport by bovine retinal capillary pericytes in culture. Exp Eye Res 1985; 41:191–199.PubMedCrossRefGoogle Scholar
  114. 114.
    Hutton JC, Schofield PJ, Williams JF, et al: Sorbitol metabolism in the retina: Accumulation of pathway intermediates in streptozotocin induced diabetes in the rat. Aust J Exp Biol Med Sci 1974; 52:361–373.PubMedCrossRefGoogle Scholar
  115. 115.
    MacGregor LC, Rosecan LR, Laties AM, et al: Microanalysis of total lipid, glucose, sorbitol, and myo-inositol in individual retinal layers of normal and alloxan diabetic rabbits. Diabetes 1984; 33:89A.Google Scholar
  116. 116.
    Li W, Shen S, Khatami M, et al: Stimulation of retinal capillary pericyte protein and collagen synthesis in culture by high-glucose concentration. Diabetes 1984; 33:785–789.PubMedCrossRefGoogle Scholar
  117. 117.
    Engerman RL, Kern TS: Experimental galactosemia produces diabetic-like retinopathy. Diabetes 1984; 33:97–100.PubMedCrossRefGoogle Scholar
  118. 118.
    Robison WG, Kador PF, Kinoshita JH: Retinal capillaries: Basement membrane thickening by galactosemia prevented with aldose reductase inhibitor. Science 1983; 221:1177–1179.PubMedCrossRefGoogle Scholar
  119. 119.
    Li W, Khatami M, Rockey JH: The effects of glucose and an aldose reductase inhibitor on the sorbitol content and collagen synthesis of bovine retinal capillary pericytes in culture. Exp Eye Res 1985; 40:439–444.PubMedCrossRefGoogle Scholar
  120. 120.
    Hotta N, Kakuta H, Fukasawa H, et al: Aldose reductase inhibitor and fructose-rich diet: Its effect on the development of diabetic retinopathy. Diabetes 1984; 33(suppl 1):199A.Google Scholar
  121. 121.
    Heath H, Hamlett YC: The sorbitol pathway: Effect of streptozotocin induced diabetes and the feeding of a sucrose-rich diet on glucose, sorbitol and fructose in the retina, blood and liver of rats. Diabetologia 1976; 12:43–46.PubMedCrossRefGoogle Scholar
  122. 122.
    Kennedy A, Frank RN, Varma SD: Aldose reductase activity in retinal and cerebral microvessels and cultured vascular cells. Invest Ophthalmol Vis Sci 1983; 24:1250–1258.PubMedGoogle Scholar
  123. 123.
    MacGregor LC, Matschinsky FM: Treatment with aldose reductase inhibitor or with myo-inositol arrests deterioration of the electroretinogram of diabetic rats. J Clin Invest 1985; 76:887–889.PubMedCrossRefGoogle Scholar
  124. 124.
    MacGregor LC, Matschinsky FM: Correlation of biochemical and electrophysiological abnormalities in retinas of experimentally diabetic animals. Diabetes 1985; 34(suppl 1):13A.Google Scholar
  125. 125.
    Yamani T: Effect of aldose reductase inhibitor on the oscillatory potential in ERG of streptozotocin diabetic rats. Folia Ophthalmol Jpn 1983; 34:2237–2244.Google Scholar
  126. 126.
    Li W, Chan S, Khatami M, et al: Inhibition of myo-inositol uptake in cultured bovine retinal capillary pericytes by D-glucose: Reversal by Sorbinil. Invest Ophthalmol Vis Sci 1985; 26(Suppl):335.Google Scholar
  127. 127.
    Krupin T, Waltman SR, Oestrich C, et al: Vitreous fluorophotometry in juvenile-onset diabetes mellitus. Arch Ophthalmol 1978; 96:812–814.PubMedGoogle Scholar
  128. 128.
    Krupin T, Waltman SR, Szewczyk P, et al: Fluorometric studies on the blood retinal barrier in experimental animals. Arch Ophthalmol 1982; 100:631–634.PubMedGoogle Scholar
  129. 129.
    Cunha-Vaz J, Mota C, Leite E, et al: Effect of aldose reductase inhibitors on the blood-retinal barrier in early diabetic retinopathy. Diabetes 1985; 34(suppl 1):109A.Google Scholar
  130. 130.
    Cunha-Vaz JG, Mota CC, Leite EC, et al: Effect of sulindac on the permeability of the blood retinal barrier in early diabetic retinopathy. Arch Ophthalmol 1985; 103:1307–1311.PubMedGoogle Scholar
  131. 131.
    Cunha-Vaz JG, Mota CC, Leite EC, et al: Effect of Sorbinil on blood-retinal barrier in early diabetic retinopathy. Diabetes 1986; 35:574–578.PubMedCrossRefGoogle Scholar
  132. 132.
    Heath H, Kang SS, Philippou D: Glucose, glucose-6-phosphate, lactate and pyruvate content of the retina, blood and liver of streptozotocin-diabetic rats fed sucrose- or starch-rich diets. Diabetologia 1975; 11:57–62.PubMedCrossRefGoogle Scholar
  133. 133.
    Hamlett YC, Heath H: The accumulation of fructose-1-phosphate in the diabetic rat retina. IRCS Med Sci 1977; 5:510.Google Scholar
  134. 134.
    Boot-Hanford R, Heath H: The effects of aldose reductase inhibitors on the metabolism of cultured monkey kidney epithelial cells. Biochem Pharmacol 1981; 30:3065–3069.CrossRefGoogle Scholar
  135. 135.
    Poulsom R, Mirrlees DJ, Earl DCN, et al: The effects of an aldose reductase inhibitor upon the sorbitol pathway, fructose-1-phosphate and lactate in the retina and nerve of streptozotocin-diabetic rats. Exp Eye Res 1983; 36:751–760.PubMedCrossRefGoogle Scholar
  136. 136.
    Schultz RO, VanHorn DL, Peters MA, et al: Diabetic keratopathy. Trans Am Ophthalmol Soc 1981; 79:180–199.PubMedGoogle Scholar
  137. 137.
    Hyndiuk RA, Kazarian EL, Schultz RO, et al: Neurotrophic corneal ulcers in diabetes mellitus. Arch Ophthalmol 1977; 95:2193–2196.PubMedGoogle Scholar
  138. 138.
    Pfister RR, Schepens CL, Lemp MA, et al: Photocoagulation keratopathy: Report of a case. Arch Ophthalmol 1971; 86:94–96.PubMedGoogle Scholar
  139. 139.
    Kanski JJ: Anterior segment complications of retinal photocoagulation. Am J Ophthalmol 1975; 79:424–427.PubMedGoogle Scholar
  140. 140.
    Perry HD, Foulks GN, Thoft RA, et al: Corneal complications after closed vitrectomy through the pars plana. Arch Ophthalmol 1978; 96:1401–1403.PubMedGoogle Scholar
  141. 141.
    Brightbill FS, Myers FL, Bresnick GN: Postvitrectomy keratopathy. Am J Ophthalmol 1978; 85:651–655.PubMedGoogle Scholar
  142. 142.
    Foulks GN, Thoft RA, Perry HD, et al: Factors related to corneal epithelial complications after closed vitrectomy in diabetes. Arch Ophthalmol 1979; 97:1076–1078.PubMedGoogle Scholar
  143. 143.
    Blankenship GW, Machemer R: Pars plana vitrectomy for the management of severe diabetic retinopathy: An analysis of results five years following surgery. Ophthalmology (Rochester) 1978; 85:553–559.Google Scholar
  144. 144.
    Faulborn J, Conway BP, Machemer R: Surgical complications of pars plana vitreous surgery. Ophthalmology (Rochester) 1978; 85:116–125.Google Scholar
  145. 145.
    Cogan DG, Kinoshita JH, Kador PF, et al: Aldose reductase and complications of diabetes. Ann Intern Med 1984; 101:82–91.PubMedGoogle Scholar
  146. 146.
    Akagi Y, Yajima Y, Kador PF, et al: Localization of aldose reductase in the human eye. Diabetes 1984; 33:562–566.PubMedCrossRefGoogle Scholar
  147. 147.
    Friend J, Snip RC, Kiorpes TC, et al: Insulin insensitivity and sorbitol production of the normal rabbit corneal epithelium in vitro. Invest Ophthalmol Vis Sci 1980; 19:913–919.PubMedGoogle Scholar
  148. 148.
    Fukushi A, Merola LO, Tanaka M, et al: Re-epithelialization of denuded corneas in diabetic rats. Exp Eye Res 1980; 31:611–621.PubMedCrossRefGoogle Scholar
  149. 149.
    Datiles MD, Kador PF, Fukui HN, et al: Corneal re-epithelialization in galactosemic rats. Invest Ophthalmol Vis Sci 1983; 24:563–569.PubMedGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1987

Authors and Affiliations

  • Margo Panush Cohen
    • 1
  1. 1.Division of Endocrinology and MetabolismUniversity of Medicine and Dentistry of New JerseyNewarkUSA

Personalised recommendations