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Poly(ADP-ribose) polymerase inhibitor PJ34 protects against UVA-induced oxidative damage in corneal endothelium

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Abstract

Fuchs endothelial corneal dystrophy (FECD) is one of the main causes for corneal endothelial blindness, which is characterized by the progressive decline of corneal endothelial cells. Poly (ADP-ribose) polymerase (PARP) was reported to be involved in cell death and apoptosis of several diseases. However, the role of PARP1 in the progression of FECD remains elusive. In the present study, we reported that UVA irradiation caused the corneal endothelial damage and corneal edema in mice, which was accompanied with the elevated activity of PARP1 and PAR. The PARP1 inhibitor PJ34 resolved the corneal edema and protected corneal endothelium from UVA-induced oxidative damage, mitochondrial dysfunction, and cell apoptosis. Mechanistically, PARP1 inhibition exerted its anti-apoptotic effects through downregulation of the phosphorylation levels of JNK1/2 and p38 MAPK and subsequently the increase of MKP-1. Our results suggest that PARP1 inhibition protects corneal endothelium from UVA-induced oxidative damage, which provides a potential alternative strategy for the therapy of FECD.

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Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

FECD:

Fuchs endothelial corneal dystrophy

CECs:

Corneal endothelial cells

ECM:

Extracellular matrix

UV:

Ultraviolet

PARP:

Poly ADP-ribose polymerase

AIF:

Apoptosis inducing factor

MKP-1:

MAPK phosphatase-1

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Acknowledgements

We thank Ph.D Qun Wang gave our work scientific suggestions.

Funding

This work was partially supported by the National Natural Science Foundation of China (81770904 and 81900834) and by the Natural Science Foundation of Shandong Province (ZR2019ZD37 and ZR2019PH110). Weiyun Shi and Qingjun Zhou were partially supported by the Taishan Scholar Program (20161059) and by the Academic Promotion Programme of Shandong First Medical University (2019PT002, 2019RC008, and 2019ZL001).

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Authors and Affiliations

  1. State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, 5 Yan’erdao Road, Qingdao, 266071, China

    Xin Wang, Chunxiao Dong, Qingjun Zhou, Haoyun Duan, Dulei Zou, Yajie Gong, Bochao Ma, Zongyi Li & Weiyun Shi

  2. Eye Hospital of Shandong First Medical University, Jinan, China

    Xin Wang & Weiyun Shi

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  1. Xin Wang
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Contributions

XW conceived and designed the experiments; CXD, QJZ and HYD conducted the statistical analysis; DLZ, YJG and BCM performed data collection; ZYL and WYS reviewed and revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Zongyi Li or Weiyun Shi.

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Wang, X., Dong, C., Zhou, Q. et al. Poly(ADP-ribose) polymerase inhibitor PJ34 protects against UVA-induced oxidative damage in corneal endothelium. Apoptosis 26, 600–611 (2021). https://doi.org/10.1007/s10495-021-01690-0

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