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R. Whiting, J. Liu, G. Bouchard, D. Unterreiner, M. Jeong, K. Narfstrom; Characterization of a Long-Term Porcine Model for Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5620.
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A porcine model was developed and characterized for long-term effects of diabetes mellitus on retinal function and structure.
Three normal pigs and six pigs with alloxan induced diabetes were studied either short-term (ST) or long-term (LT): 5-8 months (n=3) or 13-17 months (n=3) after diabetic induction. Pigs were treated periodically with insulin to maintain a manageable blood glucose level (133-600 mg/dL). Electroretinograms were performed under isofluorane anesthesia using a portable, full-field, flash system and standardized protocol. A-wave, b-wave, and oscillatory potential (OP) amplitudes were evaluated. Pigs were euthanized, eyes enucleated and fixed in 2.5% glutaraldehyde in sodium cacodylate buffer for transmission electron microscopy. Cross-sectional images of capillaries from inner nuclear (INL) and inner plexiform/ganglion cell (IPL/GCL) layers (10-20 from each layer) were obtained from each LT pig and one normal pig. For each vessel, average thickness of the basement membrane was calculated. The Tukey-Kramer method was used for pairwise comparisons of membrane thickness in both INL and IPL/GCL.
At maximum scotopic intensity, two of three LT pigs had increased a-wave amplitudes (57% and 146%) compared to average of three normal pigs. B-wave amplitudes appeared normal in the LT pigs but reduced in all ST pigs (45-58%). At standard scotopic intensity, OP amplitudes were increased in two of three LT and one ST pig and reduced in remaining pigs. Basement membrane thickness was significantly increased (p<0.001) in two of three LT pigs, both in INL and IPL/GCL. Changes in OP amplitude and basement membrane thickness occurred in the same two pigs.
Two of three LT diabetic pigs exhibited changes in both retinal function and structure. Some variability in the data may be due to insulin treatment and a wide range of blood glucose levels. This porcine model may become valuable for further research into disease mechanisms and treatment modalities.
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