Oncotarget

Research Papers:

Synergistic neuroprotective effect of rasagiline and idebenone against retinal ischemia-reperfusion injury via the Lin28-let-7-Dicer pathway

Dawei Lei, Zhengbo Shao, Xinrong Zhou and Huiping Yuan _

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Oncotarget. 2018; 9:12137-12153. https://doi.org/10.18632/oncotarget.24343

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Abstract

Dawei Lei1, Zhengbo Shao1, Xinrong Zhou1 and Huiping Yuan1

1Department of Ophthalmology, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China

Correspondence to:

Huiping Yuan, email: yuanhpmu@126.com

Keywords: rasagiline; idebenone; Lin28-let-7-Dicer; retinal ischemia-reperfusion

Received: April 04, 2017     Accepted: January 24, 2018     Published: January 30, 2018

ABSTRACT

Retinal ischemia-reperfusion (RIR) injury causes neuronal degeneration and initiates various optic nerve diseases. This study aimed to investigate the synergistic neuroprotective effect of rasagiline and idebenone against RIR injury. A combination of rasagiline and idebenone was administered intraperitoneally immediately after establishment of the RIR model. Treatment with the combination of the two drugs resulted in a significant restoration of retinal thickness and retinal ganglion cells. Apoptosis of cells in ganglion cell layers was also ameliorated, suggesting that the effect of the two drugs was synergistic and the expression of brain-derived neurotrophic factor increased. Furthermore, idebenone and rasagiline induced the expression of Lin28A and Lin28B, respectively, which resulted in a reduced expression of microRNAs in the let-7 family and an increased protein output of Dicer. The data obtained from gene overexpression and knockdown experiments indicated that let-7 and Dicer were necessary for the synergistic neuroprotective effect of the two drugs. Our findings suggested that combination therapy with rasagiline and idebenone produced a synergistic effect that ameliorated RIR injury and restored visual function. In addition, the combined treatment provided neuroprotection via enhancement of the selective regulation of let-7 by Lin28A/B. These findings implied that a treatment with the combination of rasagiline and idebenone is a feasible treatment option for optic nerve diseases.


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