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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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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.
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.
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.
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.
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