December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
Antioxidants Inhibit Diabetes-induced Activation of Retinal Nuclear Transcriptional Factor (NF-kB)
Author Affiliations & Notes
  • RA Kowluru
    Kresge Eye Inst Wayne St Univ Detroit MI
  • S Chen
    Pathology University of Western Ontario London ON Canada
  • S Chakrabarti
    Pathology University of Western Ontario London ON Canada
  • Footnotes
    Commercial Relationships   R.A. Kowluru, None; S. Chen, None; S. Chakrabarti, None. Grant Identification: JDF-I, Thomas Foundation, Michigan Eye Bank
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 2968. doi:
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      RA Kowluru, S Chen, S Chakrabarti; Antioxidants Inhibit Diabetes-induced Activation of Retinal Nuclear Transcriptional Factor (NF-kB) . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2968.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: In the pathogenesis of diabetic retinopathy retinal capillary cells undergo apoptosis that can be observed before histopathological lesions are detected. Our recent studies have shown that long-term administration of antioxidants to diabetic rats inhibits the development of the early stages of retinopathy. The purpose of this study is to investigate whether transcriptional factor, NF-kB, known to trigger genes involved in apoptosis, is activated in the retina of rats diabetic for 12-14 months, and administration of antioxidants can inhibit this activation. Methods: A group of alloxan diabetic rats received diet supplemented with a mixture of antioxidants, including Trolox, a-tocopherol, N-acetyl cysteine, ascorbic acid, b-carotene and selenium for up to 14 months. NF-kB activation, oxidative stress and NO levels were measured in the retina at 2, 8 and 14 months of diabetes. Results: 2 months of diabetes in rats resulted in retinal NF-kB activation (as detected by electrophoretic mobility shift assay), and NF-kB remained activated at 8 and 14 months of diabetes. Similarly, lipid peroxides and NO levels were elevated by over 50% in the retina of rats diabetic for 2 months. The duration of diabetes had no effect on the intensity of activation of NF-kB, severity of oxidative stress and elevation of NO. Administration of antioxidants for 2, 8 or 14 months of diabetes inhibited NF-kB activation, oxidative stress and NO elevations without ameliorating the severity of hyperglycemia. Conclusion: NF-kB is activated in retina in diabetes before either cell death or histopathology can be seen, and remains activated for the duration when the retinopathy is developing. Antioxidants might be inhibiting the development of retinopathy by inhibiting NF-kB activation.

Keywords: 554 retina • 388 diabetic retinopathy • 321 antioxidants 
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