Prion protein is essential for diabetic retinopathy-associated neovascularization

Prion protein is essential for diabetic retinopathy-associated neovascularization 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 ) is a surface protein expressed by vascular endothelial cells, and the increased expression of Pr P is associated with physiological and pathological vascularization. Nevertheless, a role for PrP 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 hyper- glycemia/diabetes itself, was significantly attenuated in PrP -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 PrP in the development of DR. Keywords Diabetic retinopathy (DR) · PrP  · Streptozocin (STZ) · Retina neovascularization Introduction Glucose homeostasis is regulated by insulin, which is pro- duced and secreted by pancreatic beta cells in response http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Angiogenesis Springer Journals

Prion protein is essential for diabetic retinopathy-associated neovascularization

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Publisher
Springer Journals
Copyright
Copyright © 2018 by Springer Science+Business Media B.V., part of Springer Nature
Subject
Biomedicine; Cancer Research; Biomedicine, general; Cell Biology; Cardiology; Ophthalmology; Oncology
ISSN
0969-6970
eISSN
1573-7209
D.O.I.
10.1007/s10456-018-9619-4
Publisher site
See Article on Publisher Site

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 ) is a surface protein expressed by vascular endothelial cells, and the increased expression of Pr P is associated with physiological and pathological vascularization. Nevertheless, a role for PrP 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 hyper- glycemia/diabetes itself, was significantly attenuated in PrP -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 PrP in the development of DR. Keywords Diabetic retinopathy (DR) · PrP  · Streptozocin (STZ) · Retina neovascularization Introduction Glucose homeostasis is regulated by insulin, which is pro- duced and secreted by pancreatic beta cells in response

Journal

AngiogenesisSpringer Journals

Published: May 30, 2018

References

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