Characterisation of diabetic retinal neuropathy in Ins2Akita mice

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Abstract

Purpose

To characterize diabetic retinal neuropathy in the Ins2Akita mouse.

Methods

Male heterozygous Ins2Akita mice (2-8 months of hyperglycemia) and C57BL/6J age-matched siblings were used in this study. Retinal function was assessed by electroretinography (ERG) and thickness measured by optical coherence tomography. Eyes were then processed for immunostaining of different neuronal cells, including photoreceptors, bipolar, horizontal, amacrine and ganglion cells.

Results

Ins2Akita mice exhibited altered scotopic ERG after 6-8 months of hyperglycemia. The reduction of outer and inner retinal thickness was observed after 2 months of diabetes. Despite no striking abnormalities were found in photoreceptors, a 40% reduction of photoreceptor synaptic ribbons was observed in Ins2Akita mice compared to age-matched controls. This was accompanied by a total depletion of horizontal cell dendritic plexus and disarrangement of rod and cone bipolar cell processes at the outer plexiform layer. In the inner retina, the number of rod and cone bipolar cells remained similar to controls, but abnormal GABAergic amacrine cell stratification and 25% reduction of rod bipolar cell axon terminals were observed. Brn3a staining revealed a 20% loss of retinal ganglion cells, which exhibited abnormal aggregates of light neurofilament. In addition, a significant retinal vascular degeneration evidenced by around 50% reductions of vascular plexus was observed in 8 month hyperglycemic Ins2Akita mice. No evidence of retinal neovascularisation was detected.

Conclusion

Ins2Akita mice present a variety of retinal neuropathies including the reduction in different types of neuronal cells and disruption of synaptic structures. The mice also develop severe retinal vascular degeneration but no neovascularisation.

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