Graphene quantum dots rescue angiogenic retinopathy via blocking STAT3/Periostin/ERK signaling

石墨烯量子点通过阻断 STAT3/Periostin/ERK 信号传导来挽救血管生成性视网膜病变

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作者:Na Zhao #, Xiao Gui #, Qian Fang #, Rui Zhang, Weiye Zhu, Haorui Zhang, Qing Li, Yukun Zhou, Jiawei Zhao, Xiao Cui, Guangping Gao, Huipeng Tang, Ni Shen, Taoyong Chen, Hongyuan Song, Wei Shen

Background

Pathological retinal angiogenesis resulting from a variety of ocular diseases including oxygen induced retinopathy, diabetic retinopathy and ocular vein occlusion, is one of the major reasons for vision loss, yet the therapeutic option is limited. Multiple nanoparticles have been reported to alleviate angiogenic retinopathy. However, the adverse effect cannot be ignored due to the relatively large scale. Graphene quantum dots (GQDs) have shown potential in drug delivery and have been proved biocompatible. In this study, Graphene quantum dots are extensively investigated for their application in angiogenic retinopathy therapy.

Conclusions

The present study indicated that GQDs could be a biocompatible anti-angiogenic nanomedicine in the treatment of pathological retinal neovascularization via disrupting periostin/ERK pathway and subsequent cell cycle.

Results

We showed that GQDs were biocompatible nanomaterials in vitro and in vivo. The nanoparticles have a dose-dependent inhibitory effect on proliferation, migration, tube formation and sprouting of human umbilical vein endothelial cells (HUVECs). Further data show that GQDs could inhibit pathological retinal neovascularization in an oxygen-induced retinopathy (OIR) model. The data of RNA sequencing suggested that periostin is involved in this process. GQDs inhibit the expression of periostin via STAT3, and further regulated cell cycle-related protein levels through ERK pathway. The signaling pathway was conformed in vivo using OIR mouse model. Conclusions: The present study indicated that GQDs could be a biocompatible anti-angiogenic nanomedicine in the treatment of pathological retinal neovascularization via disrupting periostin/ERK pathway and subsequent cell cycle.

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