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Peter Lundh von Leithner, Sabine Uhles, Vivian Lee, Christoph Ullmer, Brett Hosking, Juergen Fingerle, David Shima, Susanne Raab, Richard Foxton; Ocular phenotype of the leptin-deficient BTBR ob/ob type II diabetic mouse. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2720.
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© ARVO (1962-2015); The Authors (2016-present)
Multiple assays were performed to assess the retinal morphology, and neuronal, vascular and inflammatory pathology in the eyes of BTBR ob/ob type II obese diabetic mouse to determine its feasibility as a model of diabetic retinopathy in type 2 diabetes
Ob/ob mice were bred on the BTBR background strain to establish a model of Type 2 diabetes. Ob-/ob-, control littermates (ob-/ob+) and wild-type BTBR mice underwent standard scotopic and photopic electroretinography and DC-ERG testing beginning at 6 weeks of age up until 20 weeks. Bodyweight, blood glucose and plasma insulin levels were monitored simultaneously. In addition, histological analysis, in vivo imaging and electron microscopy was performed to assess structure and vascular permeability of the outer and inner retina
Increases in body weight and hyperglycaemia were apparent in both male and female homozygous BTBR, in comparison to heterozygous and WT mice, from 6 weeks old, and continuing for the duration of the studies. Hyperglycaemia at 6 weeks also coincided with an increase in vascular permeability, which was observed using fluorescein permeability assays. A general reductions in ERG amplitude were first detected in 6-week-old in homozygous mice, and elevated numbers of TUNEL-positive apoptotic cells in the ganglion cell layer (GCL), and outer nuclear layer (ONL) accompanied these physiological changes. We observed a strongly increased astrocyte reactivity (GFAP+), beginning in 10-week-old BTBR ob/ob mice. Finally, measurements of the thickness of the different layers of the retina of mice at 18-20 weeks old found reductions of up to 30% in the inner nuclear layer (INL), inner plexiform layer (IPL) and GCL.
BTBR ob/ob mice display vascular, neuronal, inflammatory and physiological pathological changes that can be observed in early adulthood and increases with age. Furthermore, as the mice age, the thickness of the retinal layers reduces, indicating a general degeneration of the retina. These mice may therefore represent a useful model for drug development and studying diabetic retinopathy in type II diabetes.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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