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The expression and role of PIDD in retina after optic nerve crush

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Abstract

To examine the expression of P53-induced protein with a death domain (PIDD) at retina in animal model of optic nerve crush (ONC) and to investigate the role of PIDD in retinal glial activation and NF-κB activation induced by optic nerve damage, ONC animal model was established in Sprague–Dawley rats. PIDD has three isoforms (Isof); Western blot was performed to examine the expression of PIDD (Isof-1, Isof-2, and Isof-3, respectively) in retina at different time points after ONC. Retinal glial activation is closely associated with retinal neuronal death and is monitored by the expression of GFAP+ glial cells and IBA1+ microglia, then activated microglia leads to inflammatory cytokine production. NF-kB activation in glial cells also can promote neuronal death. In our study, the role of PIDD in retinal glial activation and NF-kB activation was investigated with PIDD inhibition selectively. PIDD expression (Isof-1 and Isof-3) was dramatically increased, and peaked at 3 days after ONC, while Isof-2 did not show any difference. In the ONC animal model, the number of GFAP+ glial cells and IBA1+ microglia in retinal layers was increased significantly, inflammatory cytokine production was upregulated, and NF-κB in glial cell was also activated. Moreover, those responses induced by optic nerve damage were attenuated with PIDD inhibition, which indicated that PIDD could regulate retinal glial activation, neuro-inflammation, and NF-κB activation. These results provided the direct demonstration that the PIDD (Isof-1and Isof-3) was overexpressed in retina after ONC, and PIDD may be involved in retinal neurodegenerative diseases by regulating retinal glial activation and NF-κB activation.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (Grant Nos. 81560166, 81760178, 81760172, 81460087, and 81660168), the Natural Science Foundation of Guangxi Zhuang Autonomous Region (Grant Nos. 2018GXNSFAA281128 and 2018GXNSFBA050057), Key Technologies & Program of Guangxi (Grant No.1598012-17), and China Postdoctoral Science Foundation (Grant No. 2019M663413)

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  1. Fen Tang, Fan Xu, and Ling Cui contributed equally to this work.

Authors and Affiliations

  1. Department of Ophthalmology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi, People’s Republic of China

    Fen Tang, Fan Xu, Ling Cui, Wei Huang, Li Jiang, Lifei Chen, Wenjing He, Chaolan Shen, Hui Huang, Jian Lv, Xin Zhao, Siming Zeng, Min Li & Haibin Zhong

  2. Laboratory Animal Center, Guangxi Medical University, Nanning, 530021, China

    Yiqiang Ouyang, Xiaoping Guo & Mingyuan Zhang

  3. Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China

    Fen Tang

  4. GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, 511436, China

    Wenya Yan

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Tang, F., Xu, F., Cui, L. et al. The expression and role of PIDD in retina after optic nerve crush. J Mol Hist 51, 89–97 (2020). https://doi.org/10.1007/s10735-020-09860-1

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