Aurora kinase B disruption suppresses pathological retinal angiogenesis by affecting cell cycle progression.

Weiye Zhu, Xiao Gui, Yukun Zhou, Xin Gao, Rui Zhang, Qing Li, Haorui Zhang, Jiawei Zhao, Xiao Cui, Guangping Gao, Huipeng Tang, Chenyang Huan, Dongyan Pan, Hongyuan Song, Zhe Zhou, Wei Shen

Experimental eye research 2024 Feb

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The detrimental effects of pathological angiogenesis on the visual function are indisputable. Within a prominent role in chromosome segregation and tumor progression, aurora kinase B (AURKB) assumes a prominent role. However, its role in pathological retinal angiogenesis remains unclear. This study explores this latent mechanism. To inhibit AURKB expression, we designed specific small interfering RNAs targeting AURKB and transfected them into vascular endothelial cells. Barasertib was selected as the AURKB inhibitor. The anti-angiogenic effects of both AURKB siRNA and barasertib were assessed in vitro by cell proliferation, transwell migration, and tube formation. To evaluate the angiogentic effects of AURKB in vivo, neonatal mice were exposed to 75% oxygen followed by normoxic repositioning to establish an oxygen-induced retinopathy (OIR) model. Subsequently, phosphate-buffered saline and barasertib were administered into OIR mice via intravitreal injection. The effects of AURKB on cell cycle proteins were determined by western blot analysis. We found that AURKB was overexpressed during pathological angiogenesis. AURKB siRNA and barasertib significantly inhibited endothelial cell proliferation, migration, and tube formation in vitro. Furthermore, AURKB inhibition attenuated retinal angiogenesis in the OIR model. A possible mechanism is the disruption of cell cycle by AURKB inhibition. In conclusion, AURKB significantly influenced pathological retinal angiogenesis, thereby presenting a promising therapeutic target in ocular neovascular diseases. Copyright © 2023 Elsevier Ltd. All rights reserved.

Citation

Weiye Zhu, Xiao Gui, Yukun Zhou, Xin Gao, Rui Zhang, Qing Li, Haorui Zhang, Jiawei Zhao, Xiao Cui, Guangping Gao, Huipeng Tang, Chenyang Huan, Dongyan Pan, Hongyuan Song, Zhe Zhou, Wei Shen. Aurora kinase B disruption suppresses pathological retinal angiogenesis by affecting cell cycle progression. Experimental eye research. 2024 Feb;239:109753