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Inhibition of the adrenomedullin/nitric oxide signaling pathway in early diabetic retinopathy

  • Published:
Journal of Ocular Biology, Diseases, and Informatics

Abstract

The nitric oxide (NO) signaling pathway is integrally involved in visual processing and changes in the NO pathway are measurable in eyes of diabetic patients. The small peptide adrenomedullin (ADM) can activate a signaling pathway to increase the enzyme activity of neuronal nitric oxide synthase (nNOS). ADM levels are elevated in eyes of diabetic patients and therefore, ADM may play a role in the pathology of diabetic retinopathy. The goal of this research was to test the effects of inhibiting the ADM/NO signaling pathway in early diabetic retinopathy. Inhibition of this pathway decreased NO production in high-glucose retinal cultures. Treating diabetic mice with the PKC β inhibitor ruboxistaurin for 5 weeks lowered ADM mRNA levels and ADM-like immunoreactivity and preserved retinal function as assessed by electroretinography. The results of this study indicate that inhibiting the ADM/NO signaling pathway prevents neuronal pathology and functional losses in early diabetic retinopathy.

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Acknowledgements

We wish to sincerely thank Todd Blute for his technical assistance. This research was supported by NIH EY004785 to WDE and NIH RC1-EY020308 to JDA.

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Authors and Affiliations

  1. Department of Biology, Boston University, Boston, MA, USA

    Jan J. Blom, Thomas J. Giove & William D. Eldred

  2. Department of Ophthalmology, Children’s Hospital Boston, Boston, MA, USA

    Tara L. Favazza & James D. Akula

  3. Harvard Medical School, Boston, MA, USA

    James D. Akula

  4. Laboratory of Visual Neurobiology, Department of Biology, Boston University, 5 Cummington Street, Boston, MA, 02215, USA

    William D. Eldred

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  1. Jan J. Blom
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Correspondence to William D. Eldred.

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Blom, J.J., Giove, T.J., Favazza, T.L. et al. Inhibition of the adrenomedullin/nitric oxide signaling pathway in early diabetic retinopathy. j ocul biol dis inform 4, 70–82 (2011). https://doi.org/10.1007/s12177-011-9072-8

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  • DOI: https://doi.org/10.1007/s12177-011-9072-8

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