April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Modulation of the Adrenomedullin Signaling Pathway in Diabetic Retinopathy
Author Affiliations & Notes
  • J. J. Blom
    Biology, Boston Univeristy, Boston, Massachusetts
  • T. J. Giove
    Biology, Boston Univeristy, Boston, Massachusetts
  • M. M. Deshpande
    Biology, Boston Univeristy, Boston, Massachusetts
  • W. D. Eldred
    Biology, Boston Univeristy, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  J.J. Blom, None; T.J. Giove, None; M.M. Deshpande, None; W.D. Eldred, None.
  • Footnotes
    Support  NIH Grant EY04785
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 5362. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      J. J. Blom, T. J. Giove, M. M. Deshpande, W. D. Eldred; Modulation of the Adrenomedullin Signaling Pathway in Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5362.

      Download citation file:

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

  • Supplements

Purpose: : Diabetic retinopathy is a leading cause of vision impairment and blindness in adults. Most research has focused on the vascular pathology and its prevention. However, electrophysiological deficits and neurodegeneration occur before these vascular changes and they have a significant impact on vision. 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 calcineurin, a Ca2+ activated phosphotase that dephosphorylates neuronal nitric oxide synthase (nNOS) at Ser 847 to increase its enzyme activity. ADM levels are elevated in eyes of diabetic patients, and therefore may play a role in the pathology of diabetes and diabetic retinopathy. The goal of this research is to examine the role of the ADM signaling pathway in mice with diabetic retinopathy.

Methods: : PCR, immunocytochemistry, and NO imaging were used to determine the localization and modulation of the components of the ADM signaling pathway in two diabetic models. Retinal cultures incubated three to four days in high glucose (30mM) were used to identify early changes in an isolated system and the five week streptozotocin induced diabetes (STZID) mouse model was used for longer time points.

Results: : NO imaging showed a statistically significant increase in NO production in diabetic retinas. However, there were no significant changes in nNOS mRNA levels, and there was a significant decrease in nNOS protein levels. In retinal cultures or five week diabetic mice, there were increases in ADM-like immunoreactivity (LI) and calcineurin-LI, a decrease in phospho-nNOS(p-nNOS)-LI, and an increase in ADM message using real time PCR. When calcineurin was inhibited with FK506 (1 µM) in 3-4 day cultures, there was an increase in p-nNOS-LI in retinas incubated in 30mM glucose.

Conclusions: : These results indicated that the ADM/nNOS/NO signaling pathway was present in retina and that it was altered in diabetes. Continued exploration of this pathway will provide information how this signaling pathway can be selectively targeted to reduce the pathological changes in diabetic retinopathy.

Keywords: nitric oxide • diabetic retinopathy • signal transduction 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.