Inhibition of retinopathy and retinal metabolic abnormalities in diabetic rats with AREDS-based micronutrients

Arch Ophthalmol. 2008 Sep;126(9):1266-72. doi: 10.1001/archopht.126.9.1266.


Objectives: To investigate whether the micronutrients that were shown to reduce the risk of development of age-related macular degeneration in the Age-Related Eye Disease Study (AREDS) can have the same effect on the development of diabetic retinopathy in rats, and to understand the possible mechanisms.

Methods: Streptozotocin-induced diabetic rats received a powdered diet with or without supplemental micronutrients (ascorbic acid, vitamin E, beta-carotene, zinc, and copper). The retina was used after the rats had diabetes for 12 months to detect vascular histopathology and to measure the biochemical parameters and messenger RNA levels of the genes involved in oxidative and nitrative stress.

Results: The AREDS-based micronutrients prevented a diabetes-induced increase in the number of retinal acellular capillaries. In the same rats, micronutrients inhibited increases in retinal oxidatively modified DNA and nitrotyrosine and decreases in manganese superoxide dismutase. Diabetes-induced alterations in the messenger RNA expression of mitochondrial electron transport complex III (coenzyme Q cytochrome-c reductase) and inducible nitric oxide synthase were also prevented.

Conclusion: Age-Related Eye Disease Study-based micronutrients inhibit the development of diabetic retinopathy in rodents by inhibiting oxidative and nitrative stress.

Clinical relevance: Micronutrients that slow down the onset and progression of age-related macular degeneration have the potential to inhibit the development of diabetic retinopathy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascorbic Acid / administration & dosage
  • Body Weight
  • Copper / administration & dosage
  • Deoxyadenosines / metabolism
  • Diabetes Mellitus, Experimental / complications
  • Diabetic Retinopathy / metabolism
  • Diabetic Retinopathy / pathology
  • Diabetic Retinopathy / prevention & control*
  • Diet*
  • Eating
  • Electron Transport Complex III / genetics
  • Electron Transport Complex III / metabolism
  • Glycated Hemoglobin / analysis
  • Immunoenzyme Techniques
  • Male
  • Micronutrients / administration & dosage*
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Oxidative Stress / drug effects*
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred Lew
  • Retinal Vessels / drug effects*
  • Retinal Vessels / metabolism
  • Retinal Vessels / pathology
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism
  • Vitamin E / administration & dosage
  • Zinc Oxide / administration & dosage
  • beta Carotene / administration & dosage


  • 8-hydroxy-2'-deoxyadenosine
  • Deoxyadenosines
  • Glycated Hemoglobin A
  • Micronutrients
  • RNA, Messenger
  • beta Carotene
  • Vitamin E
  • 3-nitrotyrosine
  • Tyrosine
  • Copper
  • Nitric Oxide Synthase Type II
  • Superoxide Dismutase
  • Electron Transport Complex III
  • Ascorbic Acid
  • Zinc Oxide
  • cupric oxide