Loss of Arid1a Promotes Neuronal Survival Following Optic Nerve Injury

Xue-Qi Peng; Shang-Kun Dai; Chang-Ping Li; Pei-Pei Liu; Zhi-Meng Wang; Hong-Zhen Du; Zhao-Qian Teng; Shu-Guang Yang; Chang-Mei Liu

doi:10.3389/fncel.2020.00131

Loss of Arid1a Promotes Neuronal Survival Following Optic Nerve Injury

Front Cell Neurosci. 2020 May 15:14:131. doi: 10.3389/fncel.2020.00131. eCollection 2020.

Authors

Xue-Qi Peng^{1

2

3}, Shang-Kun Dai^{1

2

3}, Chang-Ping Li^{1

2

3}, Pei-Pei Liu^{1

3}, Zhi-Meng Wang^{1

2

3}, Hong-Zhen Du^{1

3}, Zhao-Qian Teng^{1

2

3}, Shu-Guang Yang^{1

4}, Chang-Mei Liu^{1

2

3}

Affiliations

¹ State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences (CAS), Beijing, China.
² Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.
³ Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.
⁴ Department of Orthopedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Abstract

Trauma or neurodegenerative diseases trigger the retrograde death of retinal ganglion cells (RGCs), causing an irreversible functional loss. AT-rich interaction domain 1A (ARID1A), a subunit of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex, has been shown to play crucial roles in cell homeostasis and tissue regeneration. However, its function in adult RGC regeneration remains elusive. Here, we show that optic nerve injury induces dynamic changes of Arid1a expression. Importantly, deleting Arid1a in mice dramatically promotes RGC survival, but insignificantly impacts axon regeneration after optic nerve injury. Next, joint profiling of transcripts and accessible chromatin in mature RGCs reveals that Arid1a regulates several genes involved in apoptosis and JAK/STAT signaling pathway. Thus, our findings suggest modulation of Arid1a as a potential therapeutic strategy to promote RGC neuroprotection after damage.

Keywords: Arid1a; SWI/SNF; optic nerve crush; retinal ganglion cell; survival.