Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The lens in diabetes

Eye volume 7, pages 260–275 (1993)Cite this article

Abstract

This paper reviews the changes which occur in the human lens in diabetes. They include refractive changes and cataract and age-related increases in thickness, curvatures, light scattering, autofluorescence and yellowing. The incidence of cataract is greatly increased over the age of 50 years, slightly more so in women, compared with non-diabetics. Experimental models of sugar cataract provide some evidence for the mechanism of the uncommon, but morphologically distinct, juvenile form of human diabetic cataract, where an osmotic mechanism due to sugar alcohol accumulation has been thoroughly studied in diabetic or galactose-fed rats. The discrepancy between the ready accumulation of sugar alcohol in the lens in model systems and the very slow kinetics of aldose reductase (AR) has not been satisfactorily explained and suggests that the mechanism of polyol formation is not yet fully understood in mammalian systems. The activity of AR in the human lens lies mainly in the epithelium and there appears to be a marginal expectation that sufficient sorbi-tol accumulates in cortical lens fibres to explain the lens swelling and cataract on an osmotic basis. This is even more so in the cataracts of adult diabetics, which resemble those of age-related non-diabetic cataracts in appearance. The very low levels of sorbitol in adult diabetic lenses make an osmotic mechanism for the increased risk of cataract even less likely. Other mechanisms, including glycation and oxidative stress, are discussed. The occurrence of cataract is a predictor for increased mortality in the diabetic.

Download PDF

References

  1. Giles KM, Harris JE . The accumulation of 14C from uniformly labelled glucose by the normal and diabetic rabbit lens. Am J Ophthalmol 1959;48:508.

    CAS  PubMed  Article  Google Scholar 

  2. Trayhurn P, van Heyningen R . The metabolism of amino acids in the bovine lens: their oxidation as a source of energy. Biochem J 1973;136:67–75.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  3. Kinoshita JH, Kern HL, Merola LO . Factors affecting the cation transport of calf lens. Biochim Biophys Acta 1961;47:458–67.

    CAS  PubMed  Article  Google Scholar 

  4. Kinoshita JH . Cataracts in galactosemia. The Jonas Frie-denwald Memorial Lecture. Invest Ophthalmol 1965;4:786–99.

    CAS  PubMed  Google Scholar 

  5. Gorthy WC, Morrill DJ, Anderson JW . Anterior polar cataract development in mutant Wistar rats: an ultrastructural study. In: Regnault F, Hockwin D, Courtois Y, editors. Aging of the lens. New York: Elsevier/North-Holland, 1980:207–22.

  6. Iwata S . Calcium-pump and its modulator in the lens: a review. Curr Eye Res 1985;4:299–304.

    CAS  PubMed  Article  Google Scholar 

  7. Williams MR, Duncan G, Croghan PC, Riach R, Webb SF . pH regulation in tissue-cultured bovine lens epithelial cells. J Membr Biol 1992;129:179–87.

    CAS  PubMed  Article  Google Scholar 

  8. Duncan G . Relative permeabilities of the lens membranes to sodium and potassium. Exp Eye Res 1969;8:315–25.

    CAS  PubMed  Article  Google Scholar 

  9. Weale RA . The aging eye. HK Lewis, London, 1963:1.

  10. van Heyningen R . The human lens. III. Some observations on the postmortem lens. Exp Eye Res 1972;13:155–60.

    CAS  PubMed  Article  Google Scholar 

  11. Delaye M, Tardieu A . Short-range order of crystallin proteins accounts for eye lens transparency. Nature 1983;302:415–7.

    CAS  PubMed  Article  Google Scholar 

  12. Yorio T, Bentley PJ . The effects of hyperosmotic agents on the electrical properties of the amphibian lens in vitro. Exp Eye Res 1976;22:195–208.

    CAS  PubMed  Article  Google Scholar 

  13. Lerman S, Borkman RF . Spectroscopic evaluation and classification of the normal aging and cataractous lens. Ophthalmic Res 1976;8:335–53.

    Article  Google Scholar 

  14. Wistow G, Slingsby C, Blundell T. et al. Eye-lens proteins: the three-dimensional structure of β-crystallin predicted from monomeric γ-crystallin. FEBS Lett 1981;133:9–16.

    CAS  PubMed  Article  Google Scholar 

  15. Bax B, Lapatto R, Nalini V, et al. X-ray analysis of BB2-crystallin and evolution of oligomeric lens proteins. Nature 1990;347:776–80.

    CAS  PubMed  Article  Google Scholar 

  16. Beswick HT, Harding JJ . Conformational changes induced in lens α- and γ-crystallins by modification with glucose 6-phosphate. Implications for cataract. Biochem J 1987;246:761–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. Sparrow JM, Bron AJ, Brown NAP, Ayliffe W, Hill AR . The Oxford clinical cataract classification and grading system. Int Ophthalmol 1986;9:207–25.

    CAS  Article  PubMed  Google Scholar 

  18. Bron AJ, Brown NAP . The development of the crystalline lens. In Taylor DA, Cotlier E, editors. Congenital cataract 1993.

  19. Forbes J, Brown NAP, Harris MI, Smith R, Bron AJ . Growth of the lens in childhood. Eye 1993. In press.

  20. Brown N, Tripathi R . Loss of the anterior subcapsular clear zone of the lens. Prognostic significance in cataract formation. Trans Ophthalmol Soc UK 1974;94:295.

    Google Scholar 

  21. Caruelle D, Groux-Muscatelli B, Gaudrie A, Sestier C, Coscas G, Caruelle JP, Barritault D . Immunological study of acidic fibroblast growth factor (aFGF) distribution in the eye. J Cell Biochem 1989;39:117–28.

    CAS  PubMed  Article  Google Scholar 

  22. McAvoy JW, Chamberlain CG . Growth factors in the eye. Prog Growth Factor Res 1990;2:29–43.

    CAS  PubMed  Article  Google Scholar 

  23. Bassas L, Zelenka PS, Serrano J, De Pablo F . Insulin and IGF receptors are developmentally regulated in the chick embryo eye lens. Exp Cell Res 1987;168:561–6.

    CAS  PubMed  Article  Google Scholar 

  24. Hollenberg MD . Receptors for insulin and epidermal growth factor. Relation to synthesis of DNA in cultured rabbit lens epithelium. Arch Biochem Biophys 1975;171:371–7.

    CAS  PubMed  Article  Google Scholar 

  25. Gospodarowicz D, Mescher AL, Brown KD, Birdwell CR . The role of fibroblast growth factor and epidermal growth factor in the proliferative response of the corneal and lens epithelium. Exp Eye Res 1977;25:631–49.

    CAS  PubMed  Article  Google Scholar 

  26. Blanquet PR, Patte C, Fayein N, Courtois Y . Identification and isolation from bovine epithelial lens cells of two basic fibroblast growth factor receptors that possess bFGF-enhanced phosphorylation activities. Biochem Biophys Res Commun 1989;60:1124–31.

    Article  Google Scholar 

  27. Bron AJ, Cheng H . Cataract and retinopathy. Clin Endo-crinol Metab 1986;15:971–99.

    CAS  Article  Google Scholar 

  28. Huggert A . The appearance of the band of dysjunction of the lens in diabetes mellitus. Am J Ophthalmol 1953;31:227–34.

    CAS  Google Scholar 

  29. Brown NAP, Hungerford J . The influence of the size of the lens in ocular disease. Trans Ophthalmol Soc UK 1982;102:359–63.

    PubMed  Google Scholar 

  30. Sparrow JM, Bron AJ, Brown NAP, Neil HAW . Biometry of the crystalline lens in early-onset diabetes. Br J Ophthalmol 1990;74:654–60.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. Sparrow JM, Bron AJ, Brown NAP, Neil HAW . Autofluorescence of the crystalline lens in early and late onset diabetes. Br J Ophthalmol 1992;76:25–31.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  32. Mantyjarvi M . Myopia and diabetes. A review. Acta Ophthalmol 1988;185 Suppl:82–5.

    CAS  Google Scholar 

  33. Huggert A . The appearance of the crystalline lens during different stages of transitory changes of refraction. Acta Ophthalmol 1954;32:375–89.

    CAS  Article  Google Scholar 

  34. Fledelius HC . Is myopia getting more frequent. A cross-sectional study of 1416 Danes aged 16 years. Acta Ophthalmol 1983;61:545–59.

    CAS  Article  Google Scholar 

  35. Fledelius HC . Myopia and diabetes mellitus with special reference to adult-onset myopia. Acta Ophthalmol 1986;64:33–8.

    CAS  Article  Google Scholar 

  36. Fledelius HC . Refractive change in diabetes mellitus around onset or when poorly controlled. Acta Ophthalmol 1987;65:53–7.

    CAS  Article  Google Scholar 

  37. Sparrow JM . The lens in diabetes [thesis]. University of Oxford, 1988.

  38. Duke-Elder S . Changes in refraction in diabetes mellitus. Br J Ophthalmol 1925;9:167–87.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  39. Bellows JG . The crystalline lens in diabetes mellitus. Arch Ophthalmol 1944;32:498–507.

    Article  Google Scholar 

  40. Granstrom KO . Refraktionsveranderungen bei diabetes mellitus. Acta Ophthalmol 1933;11:1–161.

    Google Scholar 

  41. Turtz CA, Turtz AI . Reversal of lens changes in early diabetes. Am J Ophthalmol 1958;46:219–20.

    CAS  PubMed  Article  Google Scholar 

  42. Marchmor MF . Transient accommodative paralysis and hyperopia in diabetes. Arch Ophthalmol 1973;89:419–21.

    Article  Google Scholar 

  43. Birnbaum F, Leu P . Akute Myopisierung und intraokularer Drucksteigerung bei Entgleisung einen juvenilen Diabetes mellitus. Klin Monatsbl Augenheilk 1975;167:613–15.

    CAS  Google Scholar 

  44. Gwinup G, Villarreal A . Relationship of serum glucose concentration to changes in refraction. Diabetes 1976;25:29–31.

    CAS  PubMed  Article  Google Scholar 

  45. Rosen M . Diabetes mellitus with relative hyperopia. Am J Ophthalmol 1956;41:680–l.

    CAS  PubMed  Article  Google Scholar 

  46. Planten JT . Physiologic optic approach of lens and cataract. Ophthalmologica 1975;171:249–53.

    CAS  PubMed  Article  Google Scholar 

  47. Eva PR, Pascoe PT, Vaughan DG . Refractive change in hyperglycaemia: hyperopia, not myopia. Br J Ophthalmol 1982;66:500–5.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  48. Fledelius HC . Refractive change in diabetes mellitus around onset or when poorly controlled. Acta Ophthalmol 1987;65:53–7.

    CAS  Article  Google Scholar 

  49. Sjolie AK, Mortensen KK, Hecht PS, Eshoj O . Visual acuity and refraction in type I diabetic patients aged 25-34 years. Acta Ophthalmol 1991;69:552.

    CAS  Article  Google Scholar 

  50. Planten JT . Changes of refraction in the adult due to changing refractive indices of the layers of the lens. Ophlhalmologica 1981;183:86–90.

    CAS  Article  Google Scholar 

  51. Planten JT, Kooijman AC, De Vries B, Woldringh J . Pathological-optic approach of cataract and lens. Ophthalmologica 1978;176:331–4.

    CAS  PubMed  Article  Google Scholar 

  52. Cheng HM, Chylack LT . Lens metabolism. In Maisel H, editor. The ocular lens: structure, function and pathology. New York: Marcel Dekker, 1985:223–64.

  53. Harding RH, Chylack LT Jr, Tung WH . The sorbinil pathway as protector of the lens against glucose-generated osmotic stress. Invest Ophthalmol Vis Sci 1981,20 ARVO Suppl: 34.

    Google Scholar 

  54. Jacob TJC, Duncan G . Glucose-induced membrane permeability changes in the lens. Exp Eye Res 1982;34:445.

    CAS  PubMed  Article  Google Scholar 

  55. Reddy VN, Schwass D, Chakrapani B, Lim CP . Biochemical changes associated with the development and reversal of galactose cataracts. Exp Eye Res 1976;23:483.

    CAS  PubMed  Article  Google Scholar 

  56. Fagerholm PP, Phillipson BT, Lindstrom B . Normal human lens — the distribution of protein. Exp Eye Res 1981;33:615–20.

    CAS  PubMed  Article  Google Scholar 

  57. Bours J, Fodisch HJ . Human fetal lens: wet and dry weight with increasing gestational age. Ophthalmic Res 1986;18:363–8.

    CAS  PubMed  Article  Google Scholar 

  58. Bours J . A reevaluation of lens wet weight, water content and water-soluble and insoluble crystallins of the ageing human lens, compared with other species. In Courtois, Fauchaux, editors. Modern trends in aging research. INSERM, 1987:373–9.

  59. Bours J, Fodisch HJ, Hockwin O . Age-related changes in water and crystallin content of the fetal and adult human lens, demonstrated by a micro sectioning technique. Ophthalmic Res 1987;19:235–9.

    CAS  PubMed  Article  Google Scholar 

  60. Huizinga A, Bot ACC, De Mul FFM, et al. Local variation in absolute water content of human and rabbit eye lenses measured by Raman micro spectroscopy. Exp Eye Res 1989;48:487–96.

    CAS  PubMed  Article  Google Scholar 

  61. Pierscionek BK, Chan DYC . Refractive index gradient of human lenses. Optom Vis Sci 1989;66:822–9.

    CAS  PubMed  Article  Google Scholar 

  62. Pierscionek BK . Presbyopia - effect of refractive index. Clin Exp Optom 1990;73:23–30.

    Article  Google Scholar 

  63. Siebinga I, Vrensen GFJM, De Mul FFM, Greve J . Age-related changes in local water and protein content of human eye lenses measured by Raman microspectroscopy. Exp Eye Res 1991;53:233–9.

    CAS  PubMed  Article  Google Scholar 

  64. Granstrom D, Swamy M, Abraham E, Takemoto L . Covalent change in the major intrinsic polypeptide (MIP26K) during cataract development in the streptozotocin-induced diabetic rat. Curr Eye Res 1989;8:589–93.

    CAS  PubMed  Article  Google Scholar 

  65. Lutze M, Bresnick GH . Lenses of diabetic patients “yellow” at an accelerated rate similar to older normals. Invest Ophthalmol Vis Sci 1991;32:194–9.

    CAS  PubMed  Google Scholar 

  66. Weale RA . Physical changes due to age and cataract. In Duncan G, editor. Mechanisms of cataract formation in the human lens. London: Academic Press, 1981.

  67. Weale RA . A biography of the eye: development, growth, age. London: HK Lewis, 1982.

  68. Weiss JN, Nishio I, Clark JI, Tanaka T, Benedek GB, Giblin FJ, Reddy VN . Early detection of cataractogenesis by laser light scattering. Invest Ophthalmol Vis Sci (ARVO Suppl) 1982:41.

  69. Bursell SE, Baker RS, Weiss JN, Haughton JF, Rand LI . Clinical photon correlation spectroscopy evaluation of human diabetic lenses. Exp Eye Res 1989;49:241–58.

    CAS  PubMed  Article  Google Scholar 

  70. Bursell SE, Karalekas DP, Craig MS . The effect of acute changes in blood glucose on lenses in diabetic and non-diabetic subjects using quasi-elastic light scattering spectroscopy. Curr Eye Res 1989;8:821–34.

    CAS  PubMed  Article  Google Scholar 

  71. Helve J, Nieminen H . Autofluorescence of the human diabetic lens in vivo. Am J Ophthalmol 1976;81:491–4.

    Article  Google Scholar 

  72. Lerman S . Radiant energy and the eye. Functional ophthalmology series. New York: MacMillan, 1980:251–301.

  73. Bleeker JC, Van Best JA, Vrij L, Van der Velde EA, Oos-terhuis A . Autofluorescence of the lens in diabetic and healthy subjects by fluorophotometry. Invest Ophthalmol Vis Sci 1986;27:791–4.

    CAS  PubMed  Google Scholar 

  74. Larsen M, Kjer B, Bendtson I, Dalgaard P, Lund-Andersen H . Lens fluorescence in relation to metabolic control of insulin-dependent diabetes mellitus. Arch Ophthalmol 1989;107:59–62.

    CAS  PubMed  Article  Google Scholar 

  75. van Wirdum E, van Best J, Bruining GJ, de Beaufort C, Oosterhuis J . Blood–retinal and blood–aqueous barrier permeability, lens autofluorescence and transmission in insulin-dependent diabetic youngsters. Graefes Arch Clin Exp Ophthalmol 1989;227:26–9.

    CAS  PubMed  Article  Google Scholar 

  76. Sparrow JM, Bron AJ, Brown NAP, Neil HAW . Biometry of the crystalline lens in late-onset diabetes: The importance of diabetes type. Br J Ophthalmol 1992;76:428–33.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  77. Zeimer RC, North RM . A new method of measuring in vivo the lens transmittance, and study of lens scatter, fluorescence and transmittance. Ophthalmic Res 1984;16:246–55.

    CAS  PubMed  Article  Google Scholar 

  78. Bensch KS, Fleming JE, Lohmann W . The role of ascorbic acid in senile cataract. Proc Natl Acad Sci USA 1985;82:7193–6.

    CAS  PubMed  Article  Google Scholar 

  79. Ortwerth BJ, Olesen PR . Ascorbic acid-induced crosslinking of lens proteins: evidence supporting a Maillard reaction. Biochim Biophys Acta 1988;956:10–22.

    CAS  PubMed  Article  Google Scholar 

  80. Brownlee M, Cerami A . The biochemistry of complications of diabetes mellitus. Ann Rev Biochem 1984;50:385–432.

    Article  Google Scholar 

  81. Sell DR, Nagaraj RH, Grandhee SK, Odetti P, Lapolla A, Fogarty J, Monnier VM . Pentosidine: a molecular marker for the cumulative damage to proteins in diabetes, aging and uremia. Diabetes Metab Rev 1991;7:239–51.

    CAS  PubMed  Article  Google Scholar 

  82. Dyer DG, Blackledge JA, Katz BM, Hull CJ, Adkisson HD, Thorpe SR, Lyons TJ, Baynes JW The Maillard reaction in vivo. Z Ernahrungswiss 1991;30:29–45.

    CAS  PubMed  Article  Google Scholar 

  83. Araki N, Ueno N, Chakrabarti B, Morino Y, Horiuchi S . Immunochemical evidence for the presence of advanced glycation end products in human lens proteins and its positive correlation with aging. J Biol Chem 1992;267:10211–14.

    CAS  PubMed  Google Scholar 

  84. Nagaraj RH, Sell DR, Prabhakaram M, Ortwerth BJ, Monnier VM . High correlation between pentosidine protein crosslinks and pigmentation implicates ascorbate in human lens senescence and cataractogenesis. Proc Natl Acad Sci USA 1991;88:10257–61.

    CAS  PubMed  Article  Google Scholar 

  85. Lyons TJ, Silvestri G, Dunn JA, Dyer DG, Baynes JW . Role of glycation in modification of lens crystallins in diabetic and non-diabetic senile cataracts. Diabetes 1991;40:1010–15.

    CAS  PubMed  Article  Google Scholar 

  86. Grandhee SK, Monnier VM . Mechanism of formation of the Maillard protein cross-link pentosidine. J Biol Chem 1991,266:11649–53.

    CAS  PubMed  Google Scholar 

  87. Baynes JW, Watkins NG, Fisher CI, et al. The Amadori product on protein: structure and reactions. In Baynes JW, Monnier V, editors. The Maillard reaction in ageing, diabetes and nutrition. New York: Alan R Liss, 1989:43–67.

  88. Harding JJ, Egerton M, Van Heyningen R, Harding RS . Diabetes, glaucoma, sex and cataract: analysis of combined data from two case–control studies. Br J Ophthalmol 1993;77:2–6.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  89. Klein BEK, Klein R, Moss SE . Prevalence of cataracts in a population-based study of persons with diabetes mellitus. Ophthalmology 1985;92:1191–6.

    CAS  PubMed  Article  Google Scholar 

  90. Klein BE, Klein R . Ocular problems in older Americans with diabetes. Clin Geriatr Med 1990;6:827–37.

    CAS  PubMed  Article  Google Scholar 

  91. Corrall RJM . Coincidental changes in conscious level and lens translucency during treatment of diabetic ketoaciosis. Br J Ophthalmol 1957;59:233–5.

    Article  Google Scholar 

  92. Vinding T, Neilson NV . Two cases of acutely developed cataract in diabetes mellitus. Acta Ophthalmol 1984;62:373–7.

    CAS  Article  Google Scholar 

  93. Chylack LT, Cheng HM . Sugar metabolism in the crys-tallin lens. Surv Ophthalmol 1978;23:26–34.

    CAS  PubMed  Article  Google Scholar 

  94. Pirie A . The biochemistry of the eye. Bibl Ophthalmol 1957;49:–287.

    Google Scholar 

  95. Green H, Bocher CA, Leopold IH . Anaerobic carbohydrate metabolism of crystalline lens. Am J Ophthalmol 1959;39:106.

    Article  Google Scholar 

  96. Mitchell HS, Dodge WM . Cataracts in rats fed on light lactose rations. J Nutr 1935;9:379.

    Article  Google Scholar 

  97. Patterson JW . Development of diabetic cataracts. Am J Ophthalmol 1952;35:68–71.

    CAS  PubMed  Article  Google Scholar 

  98. Patterson JW . Cataracts caused by carbohydrates. Am J Ophthalmol 1953;36:143–7.

    CAS  PubMed  Article  Google Scholar 

  99. Patterson JW . Cataractogenic sugars. Arch Biochem Biophys 1955;58:24–30.

    CAS  PubMed  Article  Google Scholar 

  100. van Heyningen R . The lens: metabolism and cataract. In Davson H, editor. The eye, 2nd edition. London: Academic Press, 1969:381–488.

  101. Harding JJ, Crabbe MJC . The lens: development, proteins, metabolism and cataract. In Davson H, editor. The eye, 3rd edition. London: Academic Press, 1984:207–492.

  102. van Heyningen R . The sorbitol pathway in the lens. Exp Eye Res 1962;1:396–404.

    CAS  Article  Google Scholar 

  103. Kinoshita JH . A thirty-year journey in the polyol pathway. Exp Eye Res 1990;50:567–73.

    CAS  PubMed  Article  Google Scholar 

  104. Fournier DJ, Patterson JW . Variations in ATPase activity in the development of experimental cataracts. Proc Soc Exp Biol Med 1971;137:826–32.

    CAS  PubMed  Article  Google Scholar 

  105. Reddy DVN . Amino acid transport in the lens in relationship to sugar cataracts. Invest Ophthalmol 1965;4:700–7.

    CAS  PubMed  Google Scholar 

  106. Kinoshita JH, Barber GW, Merola LO, Tung W . Changes in the levels of free amino acids and myo-inositol in the galactose-exposed lens. Invest Ophthalmol 1969;8:625–32.

    CAS  PubMed  Google Scholar 

  107. Kador PF, Zigler JS, Kinoshita JH . Alterations of lens protein synthesis in galactosemic rats. Invest Ophthalmol Vis Sci 1979;18:696.

    CAS  PubMed  Google Scholar 

  108. Kinoshita JH, Merola LO, Satoh K . Osmotic changes caused by the accumulation of dulcitol in the lenses of rats fed with galactose. Nature 1962;194:1085–7.

    CAS  PubMed  Article  Google Scholar 

  109. Collins JG, Corder CN . Aldose reductase and sorbitol dehydrogenase distribution in substructures of normal and diabetic rat lens. Invest Ophthalmol Vis Sci 1977;16:242–6.

    CAS  PubMed  Google Scholar 

  110. Jedziniak JA, Chylack LT Jr, Cheng HM, Gillis MK, Kalustian AA, Tung WH . The sorbitol pathway in the human lens: aldose reductase and polyol dehydrogenase. Invest Ophthalmol Vis Sci 1981;20:314–26.

    CAS  PubMed  Google Scholar 

  111. Akagi Y, Kador PF, Kuwabara T, Kinoshita JH . Aldose reductase in human retinal mural cells. Invest Ophthalmol Vis Sci 1983;24:1516–19.

    CAS  PubMed  Google Scholar 

  112. Varma S, Mizuno A, Kinoshita JH . Diabetic cataracts and flavonoids. Science 1977;195:205–6.

    CAS  PubMed  Article  Google Scholar 

  113. Varma SD, Kinoshita JH . The absence of cataracts in mice with congenital hyperglycemia. Exp Eye Res 1974;19:577–82.

    CAS  PubMed  Article  Google Scholar 

  114. Friedenwald JS, Rytel D . Contribution to the histopathology of cataract. Arch Ophthalmol 1955;53:825–31.

    CAS  Article  Google Scholar 

  115. von Sallmann L, Carvaggio L, Grimes P, Collins EM . Morphological study of alloxan-induced cataract. Arch Ophthalmol 1958;59:55.

    CAS  Article  Google Scholar 

  116. Kinoshita JH, Merola LO, Dikmak E . Osmotic changes in experimental galactose cataract. Exp Eye Res 1962;1:405–10.

    CAS  PubMed  Article  Google Scholar 

  117. Kinoshita JH, Merola LO . Hydration of the lens during the development of galactose cataract. Invest Ophthalmol 1964;3:577–83.

    CAS  PubMed  Google Scholar 

  118. Datiles M, Fukui H, Kuwabara T, Kinoshita JH . Galactose cataract prevention with sorbinil, an aldose reductase inhibitor: a light microscopic study. Invest Ophthalmol Vis Sci 1982;22:174–9.

    CAS  PubMed  Google Scholar 

  119. Wolff SP, Crabbe MJC . Low apparent aldose reductase activity produced by monosaccharide autoxidation. Biochem J 1985;226:625–30.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  120. Hayman S, Kinoshita JH . Isolation and properties of lens aldose reductase. J Biol Chem 1965;240:877–82.

    CAS  PubMed  Google Scholar 

  121. Crabbe MJC, Wolff S . Rat lens aldose reductase and polyol production. Biochem J 1987;247:493–6.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  122. Crabbe MJ . Aldose reductase inhibitors and cataract. Int Ophthalmol 1991;15:25–36.

    CAS  PubMed  Article  Google Scholar 

  123. Das D, Song HP, Srivastava SK . Conversion of glucose to sorbitol by aldose reductase. Invest Ophthalmol Vis Sci 1987,28 ARVO Suppl: 281.

    Google Scholar 

  124. Harding JJ . Cataract: biochemistry epidemiology and pharmacology. London: Chapman & Hall, 1991:1–333.

  125. Ansari NH, Srivastava SK . Allopurinol promotes and butylated hydroxy toluene prevents sugar-induced catar-actogenesis. Biochem Biophys Res Commun 1990;16:939–43.

    Article  Google Scholar 

  126. Sivrastava SK, Ansari NH . Prevention of sugar-induced cataractogenesis in rats by butylated hydroxytoluene. Diabetes 1988;37:1505–8.

    Article  Google Scholar 

  127. Woollard ACS, Bascal ZA, Armstrong GR, Wolff SP . Abnormal redox status without increased lipid peroxidation in sugar cataract. Diabetes 1990;39:1347–52.

    CAS  PubMed  Article  Google Scholar 

  128. Wilson DK, Bohren KM, Gabbay KH, Quiocho FA . An unlikely sugar substrate site in the 1.65A structure of the human aldose reductase holoenzyme implicated in diabetic complications. Science 1992;257:81–4.

    CAS  PubMed  Article  Google Scholar 

  129. Malone JI, Lowitt S, Cook WR . Non-osmotic diabetic cataracts. Pediatr Res 1990;27:293–6.

    CAS  PubMed  Article  Google Scholar 

  130. Trevithick JR, Creighton MO, Ross WM, Stewart-Dehann PJ, Sanwal M . Modelling cortical cataractogenesis. II. In vitro effects on the lens of agents preventing glucose- and sorbitol-induced cataracts. Can J Ophthalmol 1980;16:32–8.

    Google Scholar 

  131. Trevithick JR, Linklater HA, Mitton KP, Dzialoszynski T, Sanford SE . Modelling cortical cataractogenesis. IX. Activity of vitamin E and esters in preventing cataracts and gamma-crystallin leakage from lenses in diabetic rats. Ann NY Acad Sci 1989;570:358–71.

    CAS  PubMed  Article  Google Scholar 

  132. Ross WM, Creighton MO, Trevithick JR et al. Modelling cortical cataractogenesis. II. In vivo effects of vitamin E on cataractogenesis in diabetic rats. Can J Ophthalmol 1982;17:61–6.

    CAS  PubMed  Google Scholar 

  133. Charalampous FC, Hegsted DM . Effect of age and diet on development of cataracts in the diabetic rat. Am J Physiol 1950;161:540–4.

    CAS  PubMed  Article  Google Scholar 

  134. Patterson JW . Effect of high fat, fructose and casein diet on diabetic cataracts. Proc Soc Exp Biol Med 1955;90:–706.

    CAS  PubMed  Article  Google Scholar 

  135. Patterson JW, Patterson ME, Kinsey EV, Reddy VN . DVN: lens assays on diabetic and galactosemic rats receiving diets that modify cataract development. Invest Ophthalmol 1969;4:–98.

    Google Scholar 

  136. Hutton JC, Schofield PJ, Williams JF, Regtop HL, Hollows FC . The effect of unsaturated-fat diet on cataract formation in diabetic rats. Br J Nutr 1976;36:161.

    CAS  PubMed  Article  Google Scholar 

  137. Linklater HA, Dzialozynski T, McLeod HL, Sanford SE, Trevithick JR . Modelling cortical cataractogenesis. XL Vitamin C reduces gamma-crystallin leakage from lenses in diabetic rats. Exp Eye Res 1990;51:241–7.

    CAS  PubMed  Article  Google Scholar 

  138. Chand D, El-Agnizy HK, Richards RD, Varma SD . Sugar cataracts in vitro: implications of oxidative stress and aldose reductase I. Exp Eye Res 1982;35:491–7.

    CAS  PubMed  Article  Google Scholar 

  139. Kador PF . Overview of the current attempts towards the medical treatment of cataract. Ophthalmology 1983;90:352–64.

    CAS  Article  PubMed  Google Scholar 

  140. Gabbay KH, Merola LO, Field RA . Sorbital pathway: presence in nerve and cord with substrate accumulation in diabetes. Science 1966;151:209–10.

    CAS  PubMed  Article  Google Scholar 

  141. Greene DA, Lattimer SA, Sima AAF . Sorbitol, phospho-inoistides and sodium-potassium-ATPase in the patho-genesis of diabetic complications. N Engl J Med 1987;316:599–606.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  142. Nagata M, Hohman TC, Nishimura C, Drea CM, Oliver C, Robinson WG . Polyol and vacuole formation in cultured canine lens epithelial cells. Exp Eye Res 1989;48:667–77.

    CAS  PubMed  Article  Google Scholar 

  143. Datiles M, Kador PF, Fukui H, Hu TS, Kinoshita JH . Corneal re-epithelialization in galactosemic rats. Invest Ophthalmol Vis Sci 1983;24:563–9.

    CAS  PubMed  Google Scholar 

  144. Fukushi S, Merola LO, Tanaka M, Datiles M, Kinoshita JH . Re-epithelialization of denuded corneas in diabetic rats. Exp Eye Res 1980;31:611–21.

    CAS  PubMed  Article  Google Scholar 

  145. Kinoshita JH, Dvornik D, Draml M, Gabbay KH . The effect of an aldose reductase inhibitor on the galactose-exposed rabbit lens. Biochim Biophys Acta 1968;158:472–5.

    CAS  PubMed  Article  Google Scholar 

  146. Fukushi S, Merola LO, Kinoshita JH . Altering the course of cataracts in diabetic rats. Invest Ophthalmol Vis Sci 1980;19:313–15.

    CAS  PubMed  Google Scholar 

  147. Hu TS, Datiles M, Kinoshita JH . Reversal of galactose cataract with sorbinil in rats. Invest Ophthalmol Vis Sci 1983;24:640.

    CAS  PubMed  Google Scholar 

  148. Varma SD . Aldose reductase and the etiology of diabetic cataracts. Curr Top Eye Res 1980;3:91.

    CAS  PubMed  Google Scholar 

  149. Hockwin O, Bergeder HD, Kaiser L . Über die Galaktose-Katarakt junger Ratten nach Ganzkorper-Rontgenbestrah-lung. Ber Versamm Ophthalm Ges Heidelberg 1967;68:135–9.

    Google Scholar 

  150. Hockwin O, Bergeder HD, Ninnemann U, Fink H . Unter-suchungen zur Latenzzeit der Galaktosekatarakt von Ratten. Einfluss von Rontgenbestrahlung und Diatbeginn bei verschieden alten Tieren. Graefes Arch Klin Exp Ophthalmol 1974;189:171–8.

    CAS  Article  Google Scholar 

  151. Kodama T, Reddy VN, Gilbin F, Kinoshita JH, Harding C . Scanning electron microscopy of X-ray-induced cataract in mice on normal and galactose diet. Ophthalmic Res 1983;15:324–33.

    CAS  PubMed  Article  Google Scholar 

  152. Taura T, Gilbin FJ, Reddy VN . Further observations on the effect of galactose on the development of X-ray induced cataract in mice. Exp Eye Res 1985;41:527–43.

    CAS  PubMed  Article  Google Scholar 

  153. Rossier BC, Geering K, Kraehenbuhl JR Regulation of the sodium pump: how and why? Trends Biochem Sci 1987;12:483–7.

    CAS  Article  Google Scholar 

  154. Duncan G, Marchcantonio JM, Tomlinson J . Lens calcium and cataract. In Obrecht G, Stark LW, editors. Presbyopia research. New York: Plenum Press, 1991:33–9.

  155. Sippel TO . Changes in the water, protein and glutathione contents of the lens in the course of galactose cataract development in rats. Invest Ophthalmol 1966;5:568–75.

    CAS  PubMed  Google Scholar 

  156. Giblin FJ, Nies DE, Reddy VN . Stimulation of the hexose monophosphate shunt in rabbit lens in response to the oxidation of glutathione. Exp Eye Res 1981;33:289–98.

    CAS  PubMed  Article  Google Scholar 

  157. Hightower KR, Riley MV, McCready J . Regional distribution of calcium in alloxan diabetic rabbit lens. Curr Eye Res 1989;8:517–22.

    CAS  PubMed  Article  Google Scholar 

  158. Costagliola C, Iuliano G, Menzione M, Nesti A, Simonelli F, Rinaldi E . Systemic human diseases as oxidative risk factors in cataractogenesis. I. Diabetes. Ophthalmic Res 1988;20:308–16.

    CAS  PubMed  Article  Google Scholar 

  159. Reddy DVN, Klethi J, Kinsey VE . Studies on the crystalline lens. XII. Turnover of glycine and glutamic acid in glutathione and ophthalmic acid in the rabbit. Invest Ophthalmol 1966;5:594–600.

    CAS  PubMed  Google Scholar 

  160. Perry RE, Swamy MS, Abraham EC . Progressive changes in lens crystallin glycation and high-molecular weight aggregate formation leading to cataract development in streptozotocin-diabetic rats. Exp Eye Res 1987;44:269–82.

    CAS  PubMed  Article  Google Scholar 

  161. Blakytny R, Harding JJ . Prevention of cataract in diabetic rats by aspirin, paracetamol (acetaminophen) and ibupro-fen. Exp Eye Res 1992;54:509–18.

    CAS  PubMed  Article  Google Scholar 

  162. Kumari K, Umar S, Bansal V, Sahib MK . Inhibition of diabetes-associated complications by nucleophilic compounds. Diabetes 1991;40:1079–84.

    CAS  PubMed  Article  Google Scholar 

  163. Neilson NV, Vinding T . The prevalence of cataracts in insulin-dependent and non-insulin-dependent diabetes mellitus. An epidemiological study of diabetics treated with insulin and oral hypoglycaemic agents (OHA). Acta Ophthalmol 1984;62:595–602.

    Google Scholar 

  164. Cotlier E, Kwan B, Beatty C . The lens as an osmometer. Biochim Biophys Acta 1968;150:705.

    CAS  PubMed  Article  Google Scholar 

  165. Caird FI, Pirie A, Ramsell TG . Diabetes and the eye. Oxford: Blackwell Scientific, 1969:131.

  166. Alt A . A case of transitory lenticular opacity in both eyes in a diabetic patient. Am J Ophthalmol 1906;23:294–8.

    Google Scholar 

  167. Jackson RC . Temporary cataracts in diabetes mellitus. Br J Ophthalmol 1955;39:629–31.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  168. Brown CA, Burman D . Transient cataract in a diabetic child with hyperosmolar coma. Br J Ophthalmol 1973;57:429–33.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  169. Pirie A, van Heyningen R . The effect of diabetes on the content of sorbitol, glucose, fructose and inositol in the human lens. Exp Eye Res 1964;3:124–31.

    CAS  PubMed  Article  Google Scholar 

  170. Varma S, Schocket SS, Richards RD . Implications of aldose reductase in cataracts in human diabetes. Invest Ophthalmol Vis Sci 1979;18:237–41.

    CAS  PubMed  Google Scholar 

  171. 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 

  172. Vadot E, Guibal JP . Pathogenie de la cataracte diabetique. Bull Soc Ophthalmol Fr 1982;82:1513–14.

    CAS  Google Scholar 

  173. Lerman S, Moran M . Sorbitol generation and its inhibition by Sorbinil in the aging normal human and rabbit lens and human diabetic cataracts. Ophthalmic Res 1988;20:348–52.

    CAS  PubMed  Article  Google Scholar 

  174. Lin LR, Reddy VN, Giblin FJ, Kador PF, Kinoshita JH . Polyol accumulation in cultured human lens epithelial cells. Exp Eye Res 1991;52:93–100.

    CAS  PubMed  Article  Google Scholar 

  175. Klein R, Klein BEK, Moss SE . Visual impairment in diabetes. Ophthalmology 1984;91:l–8.

    Google Scholar 

  176. Kreines K, Rowe KW . Cataract and adult diabetes. Ohio Med J 1979;75:782–6.

    CAS  PubMed  Google Scholar 

  177. Hiller R, Sperduto RD, Ederer F . Epidemiologic associations with cataract in the 1971–1972 National Health and Nutrition Examination Survey. Am J Ophthalmol 1983;118:239–48.

    CAS  Google Scholar 

  178. Caird RI, Hutchinson M, Pirie A . Cataract and diabetes. BMJ 1964;2:665–8.

    CAS  PubMed  Article  Google Scholar 

  179. Ederer F, Hiller R, Taylor HR . Senile lens changes and diabetes in two population studies. Am J Ophthalmol 1981;91:381–95.

    CAS  PubMed  Article  Google Scholar 

  180. van Heyningen R, Harding JJ . Do aspirin-like analgesics protect against cataract? Lancet 1986;i:111–13.

    Google Scholar 

  181. Harding JJ, Egerton M, Harding RS . Protection against cataract by aspirin, paracetamol and ibuprofen. Acta Ophthalmol 1989;67:518–24.

    CAS  Article  Google Scholar 

  182. Harding JJ, Harding RS, Egerton M . Risk factors for cataract in Oxfordshire: diabetes, peripheral neuropathy, myopia, glaucoma and diarrhoea. Acta Ophthalmol 1989;67:510–17.

    CAS  Article  Google Scholar 

  183. Leske MC, Chylack LT Jr, Wu SY . The lens opacities case–control study: risk factors for cataract. Arch Ophthalmol 1991;109:244–51.

    CAS  PubMed  Article  Google Scholar 

  184. Belpoliti M, Marchaini G . Sugar alcohols in the lens epithelium of age-related cataract. Exp Eye Res 1993;56:3–6.

    CAS  PubMed  Article  Google Scholar 

  185. Pande A, Garner WH, Spector A . Glucosylation of human lens protein and cataractogenesis. Biochem Biophys Res Commun 1979;89:1260–6.

    CAS  PubMed  Article  Google Scholar 

  186. Ansari NH, Awasthi YG, Srivastava SK . Role of glycosy-lation in protein disulphide formation and cataractogenesis. Exp Eye Res 1980;31:9–19.

    CAS  PubMed  Article  Google Scholar 

  187. Kasai K, Nakamura T, Kase N et al. Increased glycosylation of proteins from cataractous lenses in diabetes. Dia-betologia 1983;25:36–8.

    CAS  Google Scholar 

  188. Garlick RL, Mazer JS, Chylack LT et al. Nonenzymatic glycation of human lens crystallin. Effect of aging and diabetes mellitus. J Clin Invest 1984;74:1742–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  189. Rao GN, Cotlier E . Free-amino groups and 5-hydro-xymethylfurfural contents in clear and cataractous human lenses. Invest Ophthalmol Vis Sci 1986;27:98–102.

    CAS  PubMed  Google Scholar 

  190. Liang JN, Hershorin LL, Chylack LT . Non-enzymatic gly-cosylation in human diabetic lens crystallins. Diabetologia 1986;29:225–8.

    CAS  PubMed  Article  Google Scholar 

  191. Gopalakrishna K, Pattabiraman TN . Effect of in vitro gly-cosylation on the solubility of lens proteins. Indian J Med Res 1986;83:210–15.

    CAS  PubMed  Google Scholar 

  192. Oimomi M, Maeda Y, Hata F, Kitamura Y, Matsumoto S, Baba S, Iga T, Yamamoto M . Glycation of cataractous lens in non-diabetic senile subjects and in diabetic patients. Exp Eye Res 1988;46:415–20.

    CAS  PubMed  Article  Google Scholar 

  193. Simonelli F, Cotticelli L, Iura A, Manna C, Nesti A, Rinaldi E, Auricchio G . The decrease of free-amino groups in senile and diabetic cataracts. Ophthalmic Res 1990;22:160–5.

    CAS  PubMed  Article  Google Scholar 

  194. Liang J, Chakrabarti B . Sugar-induced change in near ultraviolet circular dichroism of alpha-crystallin. Biochem Biophys Res Commun 1981;102:180.

    CAS  PubMed  Article  Google Scholar 

  195. Vidal P, Fernandez-Vigo J, Cabezas-Cerrato J . Low glycation level and browning in human cataracts. Acta Ophthalmol 1988;66:220–2.

    CAS  Article  Google Scholar 

  196. Bonting SJ . Na+K+ activated adenosine triphosphatase and active cation transport in the lens. Invest Ophthalmol 1965;4:723.

    CAS  PubMed  Google Scholar 

  197. Duncan G, Hightower KR, Gandolfi SA, Tomlinson J, Marchaini G . Human lens membrane cation permeability increases with age. Invest Ophthalmol Vis Sci 1989;30:1855–9.

    CAS  PubMed  Google Scholar 

  198. Takemoto L, Takehana M, Horwitz J . Covalent changes in MIP 26K during aging of the human lens membrane. Invest Ophthalmol Vis Sci 1986;27:443–6.

    CAS  PubMed  Google Scholar 

  199. Garner MH, Spector A . ATP hydrolysis kinetics by Na,K-ATPase in cataract. Exp Eye Res 1986;42:3398.

    Article  Google Scholar 

  200. Spector A, Gamer WH . Hydrogen peroxide and human cataract. Exp Eye Res 1981;33:673–81.

    CAS  PubMed  Article  Google Scholar 

  201. Simonelli F, Nesti A, Pensa M, Romano L, Savastano S, Rinaldi E, Auricchio G . Lipid peroxidation and human cataractogenesis in diabetes and severe myopia. Exp Eye Res 1989;49:181–7.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  202. Garcia-Castineiras S, Velazquez S, Marchtinez P, Torres N . Aqueous humor hydrogen peroxide Analysis with dichlo-rophenol-indophenol. Exp Eye Res 1992;55:9–19.

    CAS  PubMed  Article  Google Scholar 

  203. Kleinman NJ, Spector A . The relationship between oxida-tive stress, lens epithelial cell DNA and cataractogenesis. Exp Eye Res 1992;55 Suppl: 1 (abstract 807).

    Google Scholar 

  204. Kuchle M, Schonherr U, Dieckmann U . Risk factors for capsular rupture and vitreous loss in extracapsular cataract extraction. The Erlangen Ophthalmology Group. Fortschr Ophthalmol 1989;86:417–21.

    CAS  PubMed  Google Scholar 

  205. Laurent M, Kern P, Regnault F . Thickness and collagen metabolism of lens capsule from genetically prediabetic mice. Ophthalmic Res 1981;13:93.

    CAS  Article  Google Scholar 

  206. Benson WH, Farber ME, Caplan RJ . Increased mortality rates after cataract surgery: a statistical analysis. Ophthalmology 1988;95:1288–92.

    CAS  PubMed  Article  Google Scholar 

  207. Podgor MJ, Cassel GH, Kannel WB . Lens changes and survival in a population-based study. N Engl J Med 1985;313:1438–44.

    CAS  PubMed  Article  Google Scholar 

  208. Klein R, Moss SE, Klein BE, DeMets DL . Relation of ocular and systemic factors to survival in diabetes. Arch Intern Med 1989;149:266–72.

    CAS  PubMed  Article  Google Scholar 

  209. Cohen DL, Neil HA, Sparrow J, Thorogood M, Mann JI . Lens opacity and mortality in diabetes. Diabetic Med 1990;7:615–17.

    CAS  PubMed  Article  Google Scholar 

Download references

Author information

Affiliations

  1. Department of Ophthalmology and Nuffield Laboratory, University of Oxford, UK

    A J Bron, N A P Brown, J J Harding & R Blakytny

  2. Department of Ophthalmology, University of Bristol, UK

    J Sparrow

Authors
  1. A J Bron
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J Sparrow
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N A P Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J J Harding
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R Blakytny
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bron, A., Sparrow, J., Brown, N. et al. The lens in diabetes. Eye 7, 260–275 (1993). https://doi.org/10.1038/eye.1993.60

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/eye.1993.60

Keywords

  • Diabetic lens: thickness
  • fluorescence
  • refraction
  • cataract

Further reading

Search

Advanced search

Quick links