Prion protein is essential for diabetic retinopathy-associated neovascularization

Angiogenesis
Lingyan ZhuXiangwei Xiao

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 (PrPc) 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.

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Citations

Nov 5, 2019·Current Stem Cell Research & Therapy·L Vinod Kumar ReddyDwaipayan Sen
Feb 20, 2021·Biochemical Pharmacology·Maria Consiglia TrottaSettimio Rossi

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Methods Mentioned

BETA
ELISA
flow cytometry

Software Mentioned

NIH ImageJ
GraphPad
NIH
ImageJ
GraphPad prism

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