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SIRT1 is required for the neuroprotection of resveratrol on retinal ganglion cells after retinal ischemia-reperfusion injury in mice

Graefe's Archive for Clinical and Experimental Ophthalmology volume 258, pages 335–344 (2020)Cite this article

Abstract

Purpose

Retinal ganglion cells (RGCs) loss is closely related to visual impairment in glaucoma, so the neuroprotection on RGCs is important and novel for glaucoma research. SIRT1, a family member of sirtuins, is implicated in many crucial processes of eye diseases. The purpose of this study is to determine the neuroprotection of SIRT1 on RGCs and to investigate the underlying mechanisms of these effects in an experimental model for acute glaucoma.

Methods

Retinal ischemia-reperfusion (IR) injury was induced in C57BL/6J mice. Resveratrol (RSV, activator of SIRT1) and sirtinol (inhibitor of SIRT1) were injected intravitreally 1 day before IR injury. RGCs survival rate was quantified by immunofluorescence staining. RGCs apoptosis was evaluated by the staining of TUNEL and cleaved caspase-3, and SIRT1 level was detected by western blot. Expressions of phospho-Akt, Akt, Bax, and Bcl-2 were further determined by western blot to investigate the neuroprotective mechanisms of SIRT1.

Results

RGCs survival rates and SIRT1 levels were decreased over time after IR injury. Intravitreal injection of RSV remarkably attenuated RGCs loss in a dose-dependent manner, and the most effective concentration of RSV was 100 μM. Up-regulation of SIRT1 by RSV significantly inhibited RGCs apoptosis, increased p-Akt level, decreased Bax and cleaved caspase-3 expressions, and all these effects were diminished by 100 μM sirtinol. Moreover, there were no significant changes in total Akt and Bcl-2 levels.

Conclusion

SIRT1 activation by RSV confers neuroprotection on RGCs in retinal IR injury through the activation of Akt pathway and subsequent suppression of mitochondrial apoptotic pathway. Determination of the effective concentration of intravitreal injection of RSV also provides a theoretical basis for the clinical application of RSV.

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Acknowledgements

We thank Ying Li, Xinlan Lei, Qinqin Deng, and Xiao Zhang for their constructive scientific suggestions.

Funding

This work was funded by the National Natural Science Foundation of China (grant number 81271025).

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Author notes

  1. Jinyuan Luo and Tao He contributed equally to this work.

Affiliations

  1. Department of Ophthalmology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Hubei Province, People’s Republic of China

    Jinyuan Luo, Tao He, Jiayi Yang, Ning Yang, Zongyuan Li & Yiqiao Xing

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  1. Jinyuan Luo
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Correspondence to Yiqiao Xing.

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Luo, J., He, T., Yang, J. et al. SIRT1 is required for the neuroprotection of resveratrol on retinal ganglion cells after retinal ischemia-reperfusion injury in mice. Graefes Arch Clin Exp Ophthalmol 258, 335–344 (2020). https://doi.org/10.1007/s00417-019-04580-z

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  • DOI: https://doi.org/10.1007/s00417-019-04580-z

Keywords

  • SIRT1
  • Resveratrol
  • Retinal ganglion cell
  • Ischemia-reperfusion
  • Apoptosis
  • Neuroprotection