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Prion protein is essential for diabetic retinopathy-associated neovascularization

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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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Authors and Affiliations

  1. Department of Endocrinology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, China

    Lingyan Zhu, Jixiong Xu, Jianying Liu & Qiong Huang

  2. Department of Emergency, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China

    Ying Liu

  3. Virus Laboratory, JiangXi Province Center for Disease Control and Prevention, Nanchang, 330029, China

    Tian Gong

  4. Department of Surgery, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, 4401 Penn Ave, Pittsburgh, PA, 15224, USA

    Shane Fischbach & Xiangwei Xiao

  5. Department of Pathology and Neurology, National Prion Disease Pathology Surveillance Center, National Center for Regenerative Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA

    Wenquan Zou

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  1. Lingyan Zhu
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  2. Jixiong Xu
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Correspondence to Lingyan Zhu or Xiangwei Xiao.

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Zhu, L., Xu, J., Liu, Y. et al. Prion protein is essential for diabetic retinopathy-associated neovascularization. Angiogenesis 21, 767–775 (2018). https://doi.org/10.1007/s10456-018-9619-4

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