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• W2896473162 abstract "Loss of vascular pericytes has long been associated with the onset of diabetic retinopathy; however, mechanisms contributing to pericyte dropout are not understood. <i>Notch3</i> has been implicated in pericyte stability and survival, and linked to vascular integrity. <i>Notch3</i> mutant mice exhibit progressive loss of retinal pericytes. Given that diabetic retinopathy is associated with pericyte loss, we sought to determine whether perturbation of <i>Notch3</i> signaling contributes to diabetes-induced pericyte dropout and capillary degeneration. We utilized a pericyte-expressed LacZ transgene (<i>XlacZ4</i>) to examine pericyte loss in retinas of a type I diabetic mouse model (<i>Ins2Akita</i>) and <i>Notch3</i>-deficient mice. <i>Notch3</i> null animals showed a dramatic loss of the LacZ marker by 8 weeks of age, while <i>Ins2Akita</i> diabetic and <i>Notch3</i> heterozygous mice exhibited a much slower and subtler loss of LacZ. Although combined <i>Notch3</i> heterozygosity in <i>Ins2Akita</i> diabetic animals did not show further deficits, the trypsin digest method revealed that <i>Notch3</i> haploinsufficiency increased the formation of acellular capillaries in diabetic mice. Our data further indicate that Notch signaling is blunted in diabetic retinas and in cells exposed to hyperglycemia. These results are the first to demonstrate an association between <i>Notch3</i> signaling, pericyte loss, and diabetic retinopathy." @default.
• W2896473162 created "2018-10-26" @default.
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• W2896473162 date "2018-01-01" @default.
• W2896473162 modified "2023-10-18" @default.
• W2896473162 title "Evaluation of <b><i>Notch3</i></b> Deficiency in Diabetes-Induced Pericyte Loss in the Retina" @default.
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• W2896473162 doi "https://doi.org/10.1159/000493151" @default.
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