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Involvement of Upregulated P53-Induced Death Domain Protein in Retinal Ganglion Cells Apoptosis After Optic Nerve Crush

[ Vol. 20 , Issue. 1 ]

Author(s):

Mingyuan Zhang, Lifei Chen, Fan Xu*, Li Jiang, Wenya Yan, Bibhav Kunwar, Fen Tang, Ke Yang, Chaolan Shen, Hui Huang, Jian Lv, Chen Qin, Xiaonian Wu, Siming Zeng, Min Li, Shan Zhong* and Qi Chen*   Pages 51 - 59 ( 9 )

Abstract:


Purpose: Retinal ganglion cells (RGCs) apoptosis is a common characteristic of optic neuropathies. p53-induced protein with a death domain (PIDD) is a well-known regulator of genotoxic stress-induced apoptosis, which is constitutively cleaved into three main fragments: PIDD-N, PIDD-C and PIDD-CC. Thus, we aim to determine the physiological relevance of PIDD in RGCs apoptosis in an optic nerve crush (ONC) model.

Methods: All animals were evenly randomized into four groups: sham-control group, con-siRNA group, ONC group, and PIDD-siRNA group (ONC +PIDD-siRNA). Expressions of PIDD, caspase-2, Brn3a and tBid in ONC model were analyzed by Western blot and immunofluorescence. Mean densities of RGCs/mm2 were calculated with Fluoro-Gold (FG). Moreover, we tested the effect of PIDD-siRNA on ONC-induced RGCs apoptosis using TUNEL staining.

Results: The level of full-length PIDD was weakly present and showed no significant differences at any time points. PIDD-CC and PIDD-C were significantly up-regulated in the retina at 3 days after ONC. Meanwhile, the expression of PIDD was significantly increased in Brn3a (a marker of RGCs) positive cells, indicating that the localization of PIDD appeared to be confined to RGCs. Furthermore, inhibition of PIDD prevented RGCs apoptosis by inhibiting caspase-2 and tBid activation.

Conclusion: Taken together, PIDD may play a crucial role in RGCs apoptosis after ONC, and this process may be relevant to caspase-2 and tBid.

Keywords:

PIDD, caspase-2, retinal ganglion cells, apoptosis, optic nerve crush, RGCs.

Affiliation:

Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, Guangzhou Medical University, Guangzhou 511436, Guangzhou Medical University, Guangzhou 511436, Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi



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