The Ins2^Akita diabetic mouse lacks advanced retinopathy complications

Abstract

Purpose : The Ins2^Akita mouse model has been used as an experimental model of diabetic nephropathy and more recently as a model of diabetic retinopathy (DR). Conflicting data exists regarding the retinal abnormalities associated with DR in these mice. Here we monitored retinal changes in these mice longitudinally up to 44 weeks of age to establish if these mice display features of diabetic retinopathy.

Methods : A total of 27 Ins2^Akita diabetic and 18 wild-type littermate mice were examined longitudinally at 8, 16, 24, 36, and 44 weeks of age using optical coherence tomography (OCT), fundus photography, and fluorescein angiography. Retinas from separate animals were analyzed for leukostasis (n=12) by staining with fluorochrome-conjugated concanavalin A lectin. Ex-vivo vascular permeability was measured by FITC-dextran absorbance in the homogenized retina (n=18). Neovascularization was determined by analyzing the total retinal vascular area in flat mounts stained with isolectin B4 (n=18). Morphologic changes were measured via histopathology. Genotypes and the absence of rd8 and rd1 mutations were confirmed by PCR.

Results : Diabetes was confirmed by non-fasting blood glucose levels above 250 mg/dl. By OCT the total retinal thickness was significantly less in the Ins2^Akita diabetic mice (213.3 μm ± 1.026) compared to wild-type littermates (220.1 μm ± 1.938) up to 16 weeks of age (p = 0.0042). Fundus photography revealed no significant pathology in either the Ins2^Akita diabetic or wild-type retinas up to 44 weeks of age. No vascular changes or leakage were detected in either the Ins2^Akita diabetic or wild-type littermate controls using fluorescein angiography at any of the measured time points. Significant increases in leukostasis in retinal blood vessels were observed in the Ins2^Akita diabetic (13 ± 2.6 cells per retina) compared to wild-type animals (4.6 ± 0.92 cells per retina) at 8 weeks of age (p = 0.02). No changes in ex-vivo vascular permeability or total retinal vascular area were observed up to 36 and 44 weeks of age, respectively. Histological examinations showed no differences in retinal structure between the Ins2^Akita diabetic and wild-type littermate mice up to 44 weeks of age.

Conclusions : Our results confirm the retinal thinning and increased retinal leukostasis previously reported in the Ins2^Akita mice. No other diabetic retinopathy-associated retinal changes were observed.

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