April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Retinopathy In A Cone-Rich Rodent Model Of Type 2 Diabetes
Author Affiliations & Notes
  • Jaspreet Garcha
    Ophthalmology, University of Alberta, Edmonton, Alberta, Canada
  • Sharee Kuny
    Ophthalmology, University of Alberta, Edmonton, Alberta, Canada
  • Tyson Kinnick
    Ophthalmology and Visual Sciences, University of Iowa Health Care, Iowa City, Iowa
  • Dylan Bartel
    Ophthalmology, University of Alberta, Edmonton, Alberta, Canada
  • Michael Kreuzer
    Ophthalmology, University of Alberta, Edmonton, Alberta, Canada
  • Frederic P. Gaillard
    IPBC, University Poitiers, Poitiers, France
  • Yves Sauve
    Ophthalmology, University of Alberta, Edmonton, Alberta, Canada
  • Footnotes
    Commercial Relationships  Jaspreet Garcha, None; Sharee Kuny, None; Tyson Kinnick, None; Dylan Bartel, None; Michael Kreuzer, None; Frederic P. Gaillard, None; Yves Sauve, None
  • Footnotes
    Support  Alberta Innovates Health Solutions
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 5965. doi:
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      Jaspreet Garcha, Sharee Kuny, Tyson Kinnick, Dylan Bartel, Michael Kreuzer, Frederic P. Gaillard, Yves Sauve; Retinopathy In A Cone-Rich Rodent Model Of Type 2 Diabetes. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5965.

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

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Purpose: : To characterize the impact of diet-induced type 2 diabetes mellitus (Chaabo et al., Nutrition & Metabolism 2010, 7:29) on retina function and anatomy in a novel laboratory cone-rich rodent model of human cone function.

Methods: : Nile rats (Arvicanthis niloticus) were fed rodent chow (Prolab RMH 2000). Urine analysis confirmed the presence of glucose (0.3 to 1g/dL) and ketones (in a subset of animals). Retinas were studied functionally using the full field electroretinogram (ERG). ERG recordings in this cone-rich model (average of 35% of total photoreceptors) have the following analogies with humans: 1) photopic a-waves with amplitudes 6 times greater than in rats and mice, allowing the direct quantification of cone function and cone-driven b/a ratios; and 2) well-defined OFF responses (d-wave). Functional data were correlated with blood vessel histology (markers: Bandeiraea simplicifolia, and tomato lectin) in young and old animals.

Results: : There was progressive inner retina dysfunction as inferred by reduced b/a wave amplitude ratios and oscillatory potential (OP) amplitudes with age. The rod pathway was affected first (diminished amplitude of pure rod b-wave and related OPs), followed by cone dysfunction, consisting of (in addition to the above), reduced amplitude for the OFF response and its OPs. Isolation of cone-driven activity using a dark-adapted double flash confirmed b/a ratio reduction. Alterations in photopic and double-flash isolated cone a-wave (outer retina activity, i.e. photoreceptors) occurred at the oldest ages tested (15-18 months). Mixed rod/cone a-waves were unaffected across all ages. In aged animals, large vessels were observed extending from the inner retina towards the outer retina.

Conclusions: : Since cones are responsible for detailed and colour vision, a comprehensive characterization of their function is crucial in developing a model to study the causes and potential treatments of retinopathy caused by type 2 diabetes (a prominent cause of blindness). Our data support the relevance of the Nile rat as a model to achieve these goals. This model offers more clinical pertinence than most rodent models (rats and mice, with 1-3% cones) of acute induction of diabetes with streptozotocin.

Keywords: diabetic retinopathy • electroretinography: non-clinical • retinal neovascularization 

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