Skip to main content
SpringerLink
Log in

Capillary Degeneration in Diabetic Retinopathy

  • Chapter
  • First Online:
Visual Dysfunction in Diabetes

Part of the book series: Ophthalmology Research ((OPHRES))

  • 1041 Accesses

Abstract

The majority of clinically detectable lesions in diabetic retinopathy involve the retinal vasculature, and the severity of those vascular lesions predicts susceptibility to future vision loss from the diabetes. Capillary nonperfusion and/or degeneration are particularly important lesions of the early retinopathy, and the capillary abnormalities are believed to play a major and causal role in the progression to preretinal neovascularization that develops in some diabetic patients. An increasing number of therapeutic approaches have been identified that significantly inhibit the development of capillary obliteration in the retina. The challenge now is to identify which therapeutic approaches best inhibit the retinal vascular disease safely in patients, so that retinal sequelae of the vasoobliteration and ischemia can be inhibited in diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Engerman RL, Meyer RK. Development of retinal vasculature in rats. Am J Ophthalmol. 1965;60:628–41.

    PubMed  CAS  Google Scholar 

  2. Hughes S, Chang-Ling T. Roles of endothelial cell migration and apoptosis in vascular remodeling during development of the central nervous system. Microcirculation. 2000;7:317–33.

    PubMed  CAS  Google Scholar 

  3. Ishida S et al. Leukocytes mediate retinal vascular remodeling during development and vaso-obliteration in disease. Nat Med. 2003;9:781–8.

    PubMed  CAS  Google Scholar 

  4. Hughes S et al. Altered pericyte-endothelial relations in the rat retina during aging: implications for vessel stability. Neurobiol Aging. 2006;27:1838–47.

    PubMed  CAS  Google Scholar 

  5. Dorrell MI, Friedlander M. Mechanisms of endothelial cell guidance and vascular patterning in the developing mouse retina. Prog Retin Eye Res. 2006;25:277–95.

    PubMed  Google Scholar 

  6. Smith LE et al. Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci. 1994;35:101–11.

    PubMed  CAS  Google Scholar 

  7. Madan A, Penn JS. Animal models of oxygen-induced retinopathy. Front Biosci. 2003;8:d1030–43.

    PubMed  CAS  Google Scholar 

  8. Smith LE. Pathogenesis of retinopathy of prematurity. Semin Neonatol. 2003;8:469–73.

    PubMed  Google Scholar 

  9. Heidary G, Vanderveen D, Smith LE. Retinopathy of prematurity: current concepts in molecular pathogenesis. Semin Ophthalmol. 2009;24:77–81.

    PubMed  Google Scholar 

  10. Kohner EM, Henkind P. Correlation of fluorescein angiogram and retinal digest in diabetic retinopathy. Am J Ophthalmol. 1970;69:403–14.

    PubMed  CAS  Google Scholar 

  11. de Venecia G, Davis MD, Engerman RL. Clinicopathologic correlations in diabetic retinopathy. 1. Histology and fluorescein angiography of microaneurysms. Arch Ophthalmol. 1976;94:1766–73.

    PubMed  Google Scholar 

  12. Sleightholm MA, Aldington SJ, Arnold J, Kohner EM. Diabetic retinopathy: II. Assessment of severity and progression from fluorescein angiograms. J Diabet Complications. 1988;2:117–20.

    PubMed  CAS  Google Scholar 

  13. Shimizu K, Kobayashi Y, Muraoka K. Midperipheral fundus involvement in diabetic retinopathy. Ophthalmology. 1981;88:601–12.

    PubMed  CAS  Google Scholar 

  14. Witmer AN, Vrensen GF, Van Noorden CJ, Schlingemann RO. Vascular endothelial growth factors and angiogenesis in eye disease. Prog Retin Eye Res. 2003;22:1–29.

    PubMed  CAS  Google Scholar 

  15. Jardeleza MS, Miller JW. Review of anti-VEGF therapy in proliferative diabetic retinopathy. Semin Ophthalmol. 2009;24:87–92.

    PubMed  Google Scholar 

  16. Schlingemann RO, Witmer AN. Treatment of retinal diseases with VEGF antagonists. Prog Brain Res. 2009;175:253–67.

    PubMed  CAS  Google Scholar 

  17. Engerman RL. Pathogenesis of diabetic retinopathy. Diabetes. 1989;38:1203–6.

    PubMed  CAS  Google Scholar 

  18. Kawai SI et al. Modeling of risk factors for the degeneration of retinal ganglion cells after ischemia/reperfusion in rats: effects of age, caloric restriction, diabetes, pigmentation, and glaucoma. FASEB J. 2001;15:1285–7.

    PubMed  CAS  Google Scholar 

  19. Takahashi K, Kishi S, Muraoka K, Shimizu K. Reperfusion of occluded capillary beds in diabetic retinopathy. Am J Ophthalmol. 1998;126:791–7.

    PubMed  CAS  Google Scholar 

  20. Schroder S, Palinski W, Schmid-Schonbein GW. Activated monocytes and granulocytes, capillary nonperfusion, and neovascularization in diabetic retinopathy. Am J Pathol. 1991;139:81–100.

    PubMed  CAS  Google Scholar 

  21. Harris AG, Skalak TC, Hatchell DL. Leukocyte-capillary plugging and network resistance are increased in skeletal muscle of rats with streptozotocin-induced hyperglycemia. Int J Microcirc Clin Exp. 1994;14:159–66.

    PubMed  CAS  Google Scholar 

  22. Hatchell DL, Wilson CA, Saloupis P. Neutrophils plug capillaries in acute experimental retinal ischemia. Microvasc Res. 1994;47:344–54.

    PubMed  CAS  Google Scholar 

  23. Miyamoto K, Hiroshiba N, Tsujikawa A, Ogura Y. In vivo demonstration of increased leukocyte entrapment in retinal microcirculation of diabetic rats. Invest Ophthalmol Vis Sci. 1998;39:2190–4.

    PubMed  CAS  Google Scholar 

  24. Miyamoto K et al. Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition. Proc Natl Acad Sci USA. 1999;96:10836–41.

    PubMed  CAS  Google Scholar 

  25. Nonaka A et al. PKC-beta inhibitor (LY333531) attenuates leukocyte entrapment in retinal microcirculation of diabetic rats. Invest Ophthalmol Vis Sci. 2000;41:2702–6.

    PubMed  CAS  Google Scholar 

  26. Ogura Y. In vivo evaluation of leukocyte dynamics in the retinal and choroidal circulation. Jpn J Ophthalmol. 2000;44:322–3.

    PubMed  Google Scholar 

  27. Joussen AM et al. Leukocyte-mediated endothelial cell injury and death in the diabetic retina. Am J Pathol. 2001;158:147–52.

    PubMed  CAS  Google Scholar 

  28. Joussen AM et al. Nonsteroidal anti-inflammatory drugs prevent early diabetic retinopathy via TNF-alpha suppression. FASEB J. 2002;16:438–40.

    PubMed  CAS  Google Scholar 

  29. Kinoshita N et al. Effective and selective prevention of retinal leukostasis in streptozotocin-induced diabetic rats using gliclazide. Diabetologia. 2002;45:735–9.

    PubMed  CAS  Google Scholar 

  30. Mori F et al. Inhibitory effect of losartan, an AT1 angiotensin II receptor antagonist, on increased leucocyte entrapment in retinal microcirculation of diabetic rats. Br J Ophthalmol. 2002;86:1172–4.

    PubMed  CAS  Google Scholar 

  31. Moore TC et al. The role of advanced glycation end products in retinal microvascular ­leukostasis. Invest Ophthalmol Vis Sci. 2003;44:4457–64.

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  33. Joussen AM et al. A central role for inflammation in the pathogenesis of diabetic retinopathy. FASEB J. 2004;18:1450–2.

    PubMed  CAS  Google Scholar 

  34. Tamura H et al. Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina. Invest Ophthalmol Vis Sci. 2005;46:1440–4.

    PubMed  Google Scholar 

  35. Kinukawa Y, Shimura M, Tamai M. Quantifying leukocyte dynamics and plugging in retinal microcirculation of streptozotosin-induced diabetic rats. Curr Eye Res. 1999;18:49–55.

    PubMed  CAS  Google Scholar 

  36. Kelly LW, Barden CA, Tiedeman JS, Hatchell DL. Alterations in viscosity and filterability of whole blood and blood cell subpopulations in diabetic cats. Exp Eye Res. 1993;56:341–7.

    PubMed  CAS  Google Scholar 

  37. Lefer DJ, McLeod DS, Merges C, Lutty GA. Immunolocalization of ICAM-1 (CD54) in the posterior eye of sickle cell and diabetic patients. Invest Ophthalmol Vis Sci. 1993;34:1206.

    Google Scholar 

  38. McLeod DS, Lefer DJ, Merges C, Lutty GA. Enhanced expression of intercellular adhesion molecule-1 and P-selectin in the diabetic human retina and choroid. Am J Pathol. 1995;147:642–53.

    PubMed  CAS  Google Scholar 

  39. Zheng L, Szabo C, Kern TS. Poly(ADP-ribose) polymerase is involved in the development of diabetic retinopathy via regulation of nuclear factor-kappaB. Diabetes. 2004;53:2960–7.

    PubMed  CAS  Google Scholar 

  40. Kim SY et al. Neutrophils are associated with capillary closure in spontaneously diabetic monkey retinas. Diabetes. 2005;54:1534–42.

    PubMed  CAS  Google Scholar 

  41. Kern TS. Contributions of inflammatory processes to the development of the early stages of diabetic retinopathy. Exp Diabetes Res. 2007;2007:95103.

    PubMed  Google Scholar 

  42. Adamis AP, Berman AJ. Immunological mechanisms in the pathogenesis of diabetic retinopathy. Semin Immunopathol. 2008;30:65–84.

    PubMed  CAS  Google Scholar 

  43. Hirata F, Yoshida M, Ogura Y. High glucose exacerbates neutrophil adhesion to human retinal endothelial cells. Exp Eye Res. 2006;82:179–82.

    PubMed  CAS  Google Scholar 

  44. Zheng L et al. Critical role of inducible nitric oxide synthase in degeneration of retinal ­capillaries in mice with streptozotocin-induced diabetes. Diabetologia. 2007;50:1987–96.

    PubMed  CAS  Google Scholar 

  45. Gubitosi-Klug RA, Talahalli R, Du Y, Nadler JL, Kern TS. 5-Lipoxygenase, but not 12/15-lipoxygenase, contributes to degeneration of retinal capillaries in a mouse model of diabetic retinopathy. Diabetes. 2008;57:1387–93.

    PubMed  CAS  Google Scholar 

  46. Boeri D, Maiello M, Lorenzi M. Increased prevalence of microthromboses in retinal capillaries of diabetic individuals. Diabetes. 2001;50:1432–9.

    PubMed  CAS  Google Scholar 

  47. Yamashiro K et al. Platelets accumulate in the diabetic retinal vasculature following endothelial death and suppress blood-retinal barrier breakdown. Am J Pathol. 2003;163:253–9.

    PubMed  Google Scholar 

  48. Sun W, Gerhardinger C, Dagher Z, Hoehn T, Lorenzi M. Aspirin at low-intermediate concentrations protects retinal vessels in experimental diabetic retinopathy through non-­platelet-mediated effects. Diabetes. 2005;54:3418–26.

    PubMed  CAS  Google Scholar 

  49. Early Treatment Diabetic Retinopathy Research Group. Effects of aspirin treatment on ­diabetic retinopathy. Ophthalmology. 1991;98:757–65.

    Google Scholar 

  50. DAMAD Study Group. Effect of aspirin alone and aspirin plus dipyridamole in early diabetic retinopathy: a multicenter randomized controlled clinical trial. Diabetes. 1989;38:491–8.

    Google Scholar 

  51. Grunwald JE, DuPont J, Riva CE. Retinal haemodynamics in patients with early diabetes mellitus. Br J Ophthalmol. 1996;80:327–31.

    PubMed  CAS  Google Scholar 

  52. Konno S et al. Retinal blood flow changes in type I diabetes. A long-term follow-up study. Invest Ophthalmol Vis Sci. 1996;37:1140–8.

    PubMed  CAS  Google Scholar 

  53. Clermont AC, Bursell SE. Retinal blood flow in diabetes. Microcirculation. 2007;14:49–61.

    PubMed  CAS  Google Scholar 

  54. Pemp B, Schmetterer L. Ocular blood flow in diabetes and age-related macular degeneration. Can J Ophthalmol. 2008;43:295–301.

    PubMed  Google Scholar 

  55. Bek T. Immunohistochemical characterization of retinal glial cell changes in areas of vascular occlusion secondary to diabetic retinopathy. Acta Ophthalmol Scand. 1997;75:388–92.

    PubMed  CAS  Google Scholar 

  56. Bek T. Glial cell involvement in vascular occlusion of diabetic retinopathy. Acta Ophthalmol Scand. 1997;75:239–43.

    PubMed  CAS  Google Scholar 

  57. Schmidinger G, Maar N, Bolz M, Scholda C, Schmidt-Erfurth U. Repeated intravitreal bevacizumab (Avastin(R)) treatment of persistent new vessels in proliferative diabetic retinopathy after complete panretinal photocoagulation. Acta Ophthalmol. 2011;89:76–81.

    PubMed  CAS  Google Scholar 

  58. Mendrinos E, Donati G, Pournaras CJ. Rapid and persistent regression of severe new vessels on the disc in proliferative diabetic retinopathy after a single intravitreal injection of pegaptanib. Acta Ophthalmol. 2009;87:683–4.

    PubMed  Google Scholar 

  59. Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977–86.

    Google Scholar 

  60. United Kingdom Prospective Diabetes Study. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. Lancet. 1998;352:837–53.

    Google Scholar 

  61. Chaturvedi N et al. Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes. The EUCLID Study Group. EURODIAB Controlled Trial of Lisinopril in Insulin-Dependent Diabetes Mellitus. Lancet. 1998;351:28–31.

    PubMed  CAS  Google Scholar 

  62. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998;317:703–13.

    Google Scholar 

  63. Keech AC et al. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet. 2007;370:1687–97.

    PubMed  CAS  Google Scholar 

  64. Engerman RL, Bloodworth Jr JMB, Nelson S. Relationship of microvascular disease in diabetes to metabolic control. Diabetes. 1977;26:760–9.

    PubMed  CAS  Google Scholar 

  65. Engerman RL, Kern TS. Progression of incipient diabetic retinopathy during good glycemic control. Diabetes. 1987;36:808–12.

    PubMed  CAS  Google Scholar 

  66. Hammes H-P et al. Islet transplantation inhibits diabetic retinopathy in the sucrose-fed diabetic Cohen diabetic rat. Invest Ophthalmol Vis Sci. 1993;34:2092–6.

    PubMed  CAS  Google Scholar 

  67. Zhang JZ, Xi X, Gao L, Kern TS. Captopril inhibits capillary degeneration in the early stages of diabetic retinopathy. Curr Eye Res. 2007;32:883–9.

    PubMed  Google Scholar 

  68. Hammes HP et al. Acceleration of experimental diabetic retinopathy in the rat by omega-3 fatty acids. Diabetologia. 1996;39:251–5.

    PubMed  CAS  Google Scholar 

  69. Barile GR et al. The RAGE axis in early diabetic retinopathy. Invest Ophthalmol Vis Sci. 2005;46:2916–24.

    PubMed  Google Scholar 

  70. Mizutani M, Kern TS, Lorenzi M. Accelerated death of retinal microvascular cells in human and experimental diabetic retinopathy. J Clin Invest. 1996;97:2883–90.

    PubMed  CAS  Google Scholar 

  71. Kern TS et al. Response of capillary cell death to aminoguanidine predicts the development of retinopathy: comparison of diabetes and galactosemia. Invest Ophthalmol Vis Sci. 2000;41:3972–8.

    PubMed  CAS  Google Scholar 

  72. Kowluru RA, Tang J, Kern TS. Abnormalities of retinal metabolism in diabetes and ­experimental galactosemia. VII. Effect of long-term administration of antioxidants on the development of retinopathy. Diabetes. 2001;50:1938–42.

    PubMed  CAS  Google Scholar 

  73. Stitt A et al. The AGE inhibitor pyridoxamine inhibits development of retinopathy in experimental diabetes. Diabetes. 2002;51:2826–32.

    PubMed  CAS  Google Scholar 

  74. Asnaghi V, Gerhardinger C, Hoehn T, Adeboje A, Lorenzi M. A role for the polyol pathway in the early neuroretinal apoptosis and glial changes induced by diabetes in the rat. Diabetes. 2003;52:506–11.

    PubMed  CAS  Google Scholar 

  75. Kowluru RA, Odenbach S. Effect of long-term administration of alpha-lipoic acid on retinal capillary cell death and the development of retinopathy in diabetic rats. Diabetes. 2004;53:3233–8.

    PubMed  CAS  Google Scholar 

  76. Kern TS et al. Topical administration of nepafenac inhibits diabetes-induced retinal microvascular disease and underlying abnormalities of retinal metabolism and physiology. ­Diabetes. 2007;56:373–9.

    PubMed  CAS  Google Scholar 

  77. Zheng L, Howell SJ, Hatala DA, Huang K, Kern TS. Salicylate-based anti-inflammatory drugs inhibit the early lesion of diabetic retinopathy. Diabetes. 2007;56:337–45.

    PubMed  CAS  Google Scholar 

  78. Kern TS, Engerman RL. Vascular lesions in diabetes are distributed non-uniformly within the retina. Exp Eye Res. 1995;60:545–9.

    PubMed  CAS  Google Scholar 

  79. Tang J, Mohr S, Du Y, Kern TS. Non-uniform distribution of lesions and biochemical abnormalities within the retina of diabetic humans. Curr Eye Res. 2003;27:7–13.

    PubMed  CAS  Google Scholar 

  80. Su EN et al. Continued progression of retinopathy despite spontaneous recovery to normoglycemia in a long-term study of streptozotocin-induced diabetes in rats. Graefes Arch Clin Exp Ophthalmol. 2000;238:163–73.

    PubMed  CAS  Google Scholar 

  81. Kowluru RA. Effect of reinstitution of good glycemic control on retinal oxidative stress and nitrative stress in diabetic rats. Diabetes. 2003;52:818–23.

    PubMed  CAS  Google Scholar 

  82. Kowluru RA, Chakrabarti S, Chen S. Re-institution of good metabolic control in diabetic rats and activation of caspase-3 and nuclear transcriptional factor (NF-kappaB) in the ­retina. Acta Diabetol. 2004;41:194–9.

    PubMed  CAS  Google Scholar 

  83. Kowluru RA, Kanwar M, Kennedy A. Metabolic memory phenomenon and accumulation of peroxynitrite in retinal capillaries. Exp Diabetes Res. 2007;2007:21976.

    PubMed  Google Scholar 

  84. El-Osta A et al. Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. J Exp Med. 2008;205:2409–17.

    PubMed  CAS  Google Scholar 

  85. Feke GT, Zuckerman R, Green GJ, Weiter JJ. Response of human retinal blood flow to light and dark. Invest Ophthalmol Vis Sci. 1983;24:136–41.

    PubMed  CAS  Google Scholar 

  86. Ferrez PW, Chamot SR, Petrig BL, Pournaras CJ, Riva CR. Effect of visual stimulation on blood oxygenation in the optic nerve head of miniature pigs: a pilot study. Klin Monbl Augenheilkd. 2004;221:364–6.

    PubMed  CAS  Google Scholar 

  87. Hardarson SH et al. Oxygen saturation in human retinal vessels is higher in dark than in light. Invest Ophthalmol Vis Sci. 2009;50:2308–11.

    PubMed  Google Scholar 

  88. Riva CE, Logean E, Falsini B. Visually evoked hemodynamical response and assessment of neurovascular coupling in the optic nerve and retina. Prog Retin Eye Res. 2005;24:183–215.

    PubMed  Google Scholar 

  89. de Gooyer TE et al. Retinopathy is reduced during experimental diabetes in a mouse model of outer retinal degeneration. Invest Ophthalmol Vis Sci. 2006;47:5561–8.

    PubMed  Google Scholar 

  90. Feng Y et al. Vasoregression linked to neuronal damage in the rat with defect of polycystin-2. PLoS One. 2009;4:e7328.

    PubMed  Google Scholar 

  91. Unoki N et al. Retinal sensitivity loss and structural disturbance in areas of capillary nonperfusion of eyes with diabetic retinopathy. Am J Ophthalmol. 2007;144:755–60.

    PubMed  Google Scholar 

  92. Bresnick GH, De Venecia G, Myers FL, Harris JA, Davis MD. Retinal ischemia in diabetic retinopathy. Arch Ophthalmol. 1975;93:1300–10.

    PubMed  CAS  Google Scholar 

  93. Zhang J-Z, Kern TS. Captopril inhibits intracellular glucose accumulation in retinal cells in diabetes. Invest Ophthalmol Vis Sci. 2003;44:4001–5.

    PubMed  Google Scholar 

  94. Vincent JA, Mohr S. Inhibition of caspase-1/Interleukin-1β signaling prevents degeneration of retinal capillaries in diabetes and galactosemia. Diabetes. 2007;56:224–30.

    PubMed  CAS  Google Scholar 

  95. Krady JK et al. Minocycline reduces proinflammatory cytokine expression, microglial activation, and caspase-3 activation in a rodent model of diabetic retinopathy. Diabetes. 2005;54:1559–65.

    PubMed  CAS  Google Scholar 

  96. Du, Y. et al. Inhibition of p38 MAPK inhibits early stages of diabetic retinopathy. 2010;51:2158–64.

    Google Scholar 

  97. Sun W, Hoenh T, Gerhardinger C, Lorenzi M. Antiplatelet/anti-inflammatory drugs do not prevent early neuroretinal apoptosis and glial changes in diabetic rats (American Diabetes Association abstract). Diabetes 2004;899-P.

    Google Scholar 

  98. Behl Y et al. Diabetes-enhanced tumor necrosis factor-alpha production promotes apoptosis and the loss of retinal microvascular cells in type 1 and type 2 models of diabetic retinopathy. Am J Pathol. 2008;172:1411–8.

    PubMed  Google Scholar 

  99. Behl Y, Krothapalli P, Desta T, Roy S, Graves DT. FOXO1 plays an important role in enhanced microvascular cell apoptosis and microvascular cell loss in type 1 and type 2 diabetic rats. Diabetes. 2009;58:917–25.

    PubMed  CAS  Google Scholar 

  100. Dagher Z et al. Studies of rat and human retinas predict a role for the polyol pathway in human diabetic retinopathy. Diabetes. 2004;53:2404–11.

    PubMed  CAS  Google Scholar 

  101. Ramana KV, Bhatnagar A, Srivastava SK. Inhibition of aldose reductase attenuates TNF-alpha-induced expression of adhesion molecules in endothelial cells. FASEB J. 2004;18:1209–18.

    PubMed  CAS  Google Scholar 

  102. Ramana KV, Friedrich B, Srivastava S, Bhatnagar A, Srivastava SK. Activation of nuclear factor-kappaB by hyperglycemia in vascular smooth muscle cells is regulated by aldose reductase. Diabetes. 2004;53:2910–20.

    PubMed  CAS  Google Scholar 

  103. Ramana KV et al. Endotoxin-induced cardiomyopathy and systemic inflammation in mice is prevented by aldose reductase inhibition. Circulation. 2006;114:1838–46.

    PubMed  CAS  Google Scholar 

  104. Tammali R, Ramana KV, Singhal SS, Awasthi S, Srivastava SK. Aldose reductase regulates growth factor-induced cyclooxygenase-2 expression and prostaglandin e2 production in human colon cancer cells. Cancer Res. 2006;66:9705–13.

    PubMed  CAS  Google Scholar 

  105. Hammes HP et al. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat Med. 2003;9:294–9.

    PubMed  CAS  Google Scholar 

  106. Murakoshi M et al. Pleiotropic effect of pyridoxamine on diabetic complications via CD36 expression in KK-Ay/Ta mice. Diabetes Res Clin Pract. 2009;83:183–9.

    PubMed  CAS  Google Scholar 

  107. Hammes H-P, Martin S, Federlin K, Geisen K, Brownlee M. Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy. Proc Natl Acad Sci USA. 1991;88:11555–8.

    PubMed  CAS  Google Scholar 

  108. Hammes H-P et al. Aminoguanidine inhibits the development of accelerated diabetic retinopathy in the spontaneous hypertensive rat. Diabetologia. 1994;37:32–5.

    PubMed  CAS  Google Scholar 

  109. Hoffmann J et al. Tenilsetam prevents early diabetic retinopathy without correcting pericyte loss. Thromb Haemost. 2006;95:689–95.

    PubMed  CAS  Google Scholar 

  110. Hammes HP, Bartmann A, Engel L, Wulfroth P. Antioxidant treatment of experimental diabetic retinopathy in rats with nicanartine. Diabetologia. 1997;40:629–34.

    PubMed  CAS  Google Scholar 

  111. Kowluru RA, Kanwar M, Chan PS, Zhang JP. Inhibition of retinopathy and retinal metabolic abnormalities in diabetic rats with AREDS-based micronutrients. Arch Ophthalmol. 2008;126:1266–72.

    PubMed  Google Scholar 

  112. Hammes H-P, Federoff HJ, Brownlee M. Nerve growth factor prevents both neuroretinal programmed cell death and capillary pathology in experimental diabetes. Mol Med. 1995;1:527–34.

    PubMed  CAS  Google Scholar 

  113. Sofroniew MV, Howe CL, Mobley WC. Nerve growth factor signaling, neuroprotection, and neural repair. Annu Rev Neurosci. 2001;24:1217–81.

    PubMed  CAS  Google Scholar 

  114. Robison Jr WG, Tillis TN, Laver N, Kinoshita JH. Diabetes-related histopathologies of the rat retina prevented with an aldose reductase inhibitor. Exp Eye Res. 1990;50:355–66.

    PubMed  CAS  Google Scholar 

  115. Robison Jr WG, Laver NM, Jacot JL, Glover JP. Sorbinil prevention of diabetic-like retinopathy in the galactose-fed rat model. Invest Ophthalmol Vis Sci. 1995;36:2368–80.

    PubMed  Google Scholar 

  116. Joussen AM et al. TNF-alpha mediated apoptosis plays an important role in the development of early diabetic retinopathy and long-term histopathological alterations. Mol Vis. 2009;15:1418–28.

    PubMed  CAS  Google Scholar 

  117. Berkowitz BA, Gradianu M, Bissig D, Kern TS, Roberts R. Retinal ion regulation in a mouse model of diabetic retinopathy: natural history and the effect of Cu/Zn superoxide dismutase overexpression. Invest Ophthalmol Vis Sci. 2009;50:2351–8.

    PubMed  Google Scholar 

  118. Kanwar M, Chan PS, Kern TS, Kowluru RA. Oxidative damage in the retinal mitochondria of diabetic mice: possible protection by superoxide dismutase. Invest Ophthalmol Vis Sci. 2007;48:3805–11.

    PubMed  Google Scholar 

Download references

Acknowledgment

This work was funded by PHS grant EY00300 and a grant from the Medical Research Service of the Department of Veteran Affairs.

Author information

Authors and Affiliations

  1. Departments of Medicine and Ophthalmology, Case Western Reserve University, Cleveland, OH, USA

    Timothy S. Kern

Authors
  1. Timothy S. Kern
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Timothy S. Kern .

Editor information

Editors and Affiliations

  1. Milton S. Hershey Medical Center, Dept. Neural and Behavioral Sciences, Penn State College of Medicine, University Drive 500, Hershey, 17033, Pennsylvania, USA

    Joyce Tombran-Tink

  2. Milton S. Hershey Medical Center, Dept. Neural and Behavioral Sciences, Penn State College of Medicine, University Drive 500, Hershey, 17033, Pennsylvania, USA

    Colin J. Barnstable

  3. Molecular and Integrative Physiology, Ophthalmology and Visual Sciences, Kellogg Eye Center, Wall Street 1000, Ann Arbor, 17033-2390, Michigan, USA

    Thomas W. Gardner

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Kern, T.S. (2012). Capillary Degeneration in Diabetic Retinopathy. In: Tombran-Tink, J., Barnstable, C., Gardner, T. (eds) Visual Dysfunction in Diabetes. Ophthalmology Research. Springer, New York, NY. https://doi.org/10.1007/978-1-60761-150-9_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-150-9_9

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-60761-149-3

  • Online ISBN: 978-1-60761-150-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation