Profiling miRNAs in a hyperglycemic and hypoinsulinemic Ins2Akita mouse model

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Diabetic retinopathy (DR) is a leading cause of blindness. Our goal is to identify novel genetic targets involved in DR. microRNAs (miRNAs) are non-coding RNAs that regulate gene expression. The purpose of this study is to characterize the in vivo perturbations of retinal miRNAs in a hyperglycemic and hypoinsulinemic mouse model. Here, we characterize the vascular and macroscopic anatomic properties of the Ins2Akita mouse and then profiled the miRNA abundance longitudinally, using a cost effective multiplexed next generation sequencing method.


Heterozygous male Ins2Akita with a mutation in the insulin 2 gene, were age matched with C57BL6/J mice. We analyzed: vascular permeability by Evans blue extravasation, performed fundus photography and fluorescein angiography, and surveyed for functional visual impairment by electroretinography (ERG). Then, we measured miRNA abundance in the retina and choroid/retinal pigmented epithelium (RPE) at several time points using multiplexed libraries of Ins2Akita and wild-type mice at 1 and 3 months of age.


Morphological changes and fluorescein angiogram abnormalities were identified in the retinas of Ins2Akita at 1 and 3 months. We observed substantially increased vascular permeability in Ins2Aktia retina at 3 months. Functional changes were observed by ERG at 6 months of age. miRNA profiles were generated for Ins2Akita and control mice (1 and 3 months), which showed substantial down regulation of several miRNAs including miR-126 and miR-143 in the choroid/RPE, when compared to control.


miRNAs identified offer potential targets for genetic modulation in hyperglycemic induced pathology in the eye

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