September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Regulation of copper metabolism in the diabetic retina and effects of treatment with the Cu(II) chelator triethylenetetramine (TETA)
Author Affiliations & Notes
  • Sandra Callagy
    Centre for Ophthalmology and Vision Sciences, Institute of Human Development, University of Manchester, Manchester, England, United Kingdom
    Centre for Advanced Discovery and Experimental Therapeutics, Central Manchester University Hospitals NHS Foundation Trust (CMFT), Manchester, United Kingdom
  • Stephanie Church
    Centre for Advanced Discovery and Experimental Therapeutics, Central Manchester University Hospitals NHS Foundation Trust (CMFT), Manchester, United Kingdom
  • Nicole Brace
    Centre for Ophthalmology and Vision Sciences, Institute of Human Development, University of Manchester, Manchester, England, United Kingdom
  • Paul Begley
    Centre for Advanced Discovery and Experimental Therapeutics, Central Manchester University Hospitals NHS Foundation Trust (CMFT), Manchester, United Kingdom
  • Natalie Gardiner
    Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom
  • Garth Cooper
    Centre for Advanced Discovery and Experimental Therapeutics, Central Manchester University Hospitals NHS Foundation Trust (CMFT), Manchester, United Kingdom
    School of Biological Sciences, Faculty of Science, and Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
  • Paul N Bishop
    Centre for Ophthalmology and Vision Sciences, Institute of Human Development, University of Manchester, Manchester, England, United Kingdom
    Centre for Advanced Discovery and Experimental Therapeutics, Central Manchester University Hospitals NHS Foundation Trust (CMFT), Manchester, United Kingdom
  • Footnotes
    Commercial Relationships   Sandra Callagy, None; Stephanie Church, None; Nicole Brace, None; Paul Begley, None; Natalie Gardiner, None; Garth Cooper, PhilERA (C), Spouse - PhilERA (P); Paul Bishop, None
  • Footnotes
    Support  Fight for Sight grant R115945
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5440. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Sandra Callagy, Stephanie Church, Nicole Brace, Paul Begley, Natalie Gardiner, Garth Cooper, Paul N Bishop; Regulation of copper metabolism in the diabetic retina and effects of treatment with the Cu(II) chelator triethylenetetramine (TETA). Invest. Ophthalmol. Vis. Sci. 2016;57(12):5440.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Dysregulation of copper (Cu) homeostasis has been implicated in the pathology of diabetic organ damage. Free Cu ions may interact with peroxidases and superoxides to catalyse reactive oxygen species production. Oral treatment with the Cu(II) chelator triethylenetetramine (TETA) has been shown to reverse structural and functional changes in the diabetic heart and kidney. We hypothesised that there is also impaired Cu homeostasis in the diabetic retina and this contributes to the oxidative stress that has been observed in this condition. Therefore, the regulation of Cu metabolism was investigated in the diabetic retina as well as the potential for therapeutic or toxic effects from TETA treatment.

Methods : Male Sprague Dawley rats were administered saline or 55mg/kg of streptozotocin (STZ). STZ-treated rats were split into untreated and TETA-treated groups and maintained for 16 weeks. 30mg/rat/day of TETA-disuccinate was administered via drinking water. Eyes were enucleated and retinas were dissected and processed for analysis. mRNA expression of copper transporters and oxidative stress mediators was analysed using rt-qPCR.

Results : We demonstrate that mRNA expression of ceruloplasmin, a copper-bound iron ferroxidase, is increased during hyperglycaemia compared to control (p < 0.0001) and this was partially normalised by TETA treatment (p < 0.001). Metallothionein 1 and 2 mRNA expression was increased during hyperglycaemia compared to controls (p < 0.0001) and Metallothionein 2 expression was further increased by TETA treatment compared to untreated diabetic (p < 0.05). ATP7A expression was significantly decreased in TETA-treated retinas compared to both untreated control and diabetic retinas (p < 0.05).

Conclusions : The observed changes to ceruloplasmin expression suggest that there is increased copper in the diabetic retina which was partially normalised by TETA-treatment. Changes to metallothioneins may indicate a protective effect, as these sequester and store reactive Cu ions. Studies are ongoing to confirm that these changes are present at a protein level as is quantification of trace metals in the retina using inductively coupled plasma mass spectrometry.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

×
×

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.

×