Prion protein is essential for diabetic retinopathy-associated neovascularization.
Lingyan ZhuJixiong XuYing LiuTian GongJianying LiuQiong HuangShane FischbachWenquan ZouXiangwei XiaoPublished in: Angiogenesis (2018)
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.
Keyphrases
- diabetic retinopathy
- vascular endothelial growth factor
- optical coherence tomography
- endothelial cells
- diabetic rats
- editorial comment
- high glucose
- type diabetes
- oxidative stress
- cardiovascular disease
- binding protein
- protein protein
- poor prognosis
- signaling pathway
- skeletal muscle
- high fat diet induced
- metabolic syndrome
- small molecule
- density functional theory
- long non coding rna
- wild type