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Zongchao Han, Junjing Guo, Shannon M. Conley, Muna I. Naash; Retinal Angiogenesis in the Ins2Akita Mouse Model of Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2013;54(1):574-584. doi: https://doi.org/10.1167/iovs.12-10959.
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Diabetic retinopathy (DR) is the leading cause of blindness among working age adults and does not have any curative treatments. Although chemical- and injury-induced models of retinal neovascularization exist, the need for a genetic model that closely simulates the DR pathologic process is great.
Here we characterize the development of the retinal disease phenotype in a genetic model of type 1 diabetes, the Ins2Akita mouse, using structural, biochemical, molecular biological, and functional techniques.
This model exhibits hyperglycemia by 2 months of age and by 6 months we detect retinal complications in Ins2Akita males, including early signs of vascular damage consistent with DR, specifically the appearance of pericyte ghosts, vascular leakage, and microaneurysm formation. By 9 months of age, these changes are accompanied by later vascular signs of DR, specifically retinal neovascularization, formation of new capillary beds, and the presence of new blood vessels abnormally localized in the outer plexiform layer. Consistent with the debilitating effects of such vasculopathy, we also observe increased retinal apoptosis and decreased retinal function measured by electroretinogram.
These data indicate that the Ins2Akita mouse is a good model for later-onset DR, modeling both early and some late disease signs. Furthermore, this work suggests that this model may be suitable for testing and development of targeted DR therapies.
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