451. Prion protein is essential for diabetic retinopathy-associated neovascularization.
- Author
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Zhu L, Xu J, Liu Y, Gong T, Liu J, Huang Q, Fischbach S, Zou W, and Xiao X
- Subjects
- Animals, Diabetes Mellitus, Experimental genetics, Diabetes Mellitus, Experimental pathology, Diabetic Retinopathy genetics, Diabetic Retinopathy pathology, Mice, Mice, Knockout, PrPC Proteins genetics, Retinal Neovascularization genetics, Retinal Neovascularization pathology, Diabetes Mellitus, Experimental metabolism, Diabetic Retinopathy metabolism, PrPC Proteins metabolism, Retinal Neovascularization metabolism
- Abstract
Diabetic retinopathy (DR), a major complication of diabetes caused by vascular damage and pathological proliferation of retinal vessels, often progresses to vision loss. Vascular endothelial growth factor (VEGF) signaling plays a pivotal role in the development of DR, but the exact underlying molecular mechanisms remain ill-defined. Cellular prion protein (PrP
c ) is a surface protein expressed by vascular endothelial cells, and the increased expression of PrPc is associated with physiological and pathological vascularization. Nevertheless, a role for PrPc in the development of DR has not been appreciated. Here, we addressed this question. We found that the development of streptozocin (STZ)-induced DR, but not the STZ-induced hyperglycemia/diabetes itself, was significantly attenuated in PrPc -KO mice, compared to control wildtype (WT) mice, evident by measurement of retinal vascular leakage, retinal neovascularization, a retinopathy score and visual acuity assessment. Moreover, the attenuation of DR severity seemingly resulted from attenuation of retinal neovascularization via VEGF/ras/rac signaling. Together, our study suggests a previously unappreciated role for PrPc in the development of DR.- Published
- 2018
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