title: Long non-coding RNA MALAT1 regulates retinal neurodegeneration through CREB signaling.
abstract: The nervous and vascular systems, although functionally different, share many common regulators of function maintenance. Long non-coding RNAs (lncRNAs) are important players in many biological processes and human disorders. We previously identified a role of MALAT1 in microvascular dysfunction. However, its role in neurodegeneration is still unknown. Here, we used the eye as the model to investigate the role of MALAT1 in retinal neurodegeneration. We show that MALAT1 expression is significantly up-regulated in the retinas, Müller cells, and primary retinal ganglion cells (RGCs) upon stress. MALAT1 knockdown reduces reactive gliosis, Müller cell activation, and RGC survival in vivo and in vitro MALAT1-CREB binding maintains CREB phosphorylation by inhibiting PP2A-mediated dephosphorylation, which leads to continuous CREB signaling activation. Clinical and animal experimentation suggests that MALAT1 dysfunction is implicated in neurodegenerative processes and several human disorders. Collectively, this study reveals that MALAT1 might regulate the development of retinal neurodegeneration through CREB signaling.
authors.affiliation: Eye Hospital, Nanjing Medical University, Nanjing, China The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yao
authors.affiliation: Eye Hospital, Nanjing Medical University, Nanjing, China The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Xiao-Qun
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: Eye Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Eye Hospital, Nanjing Medical University, Nanjing, China The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Shan
authors.affiliation: Eye Hospital, Nanjing Medical University, Nanjing, China The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.affiliation: Eye Hospital, Nanjing Medical University, Nanjing, China The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Yang-Ning-Zhi
authors.initials: YN
authors.lastname: Wang
authors.affiliation: Eye Hospital, Nanjing Medical University, Nanjing, China The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Mu-Di
authors.initials: MD
authors.lastname: Yao
authors.affiliation: Eye Hospital, Nanjing Medical University, Nanjing, China The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Eye Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Xiu-Miao
authors.initials: XM
authors.lastname: Li
authors.affiliation: Eye Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Eye Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Liu
authors.affiliation: Department of Neurology, Jiangsu Province Hospital, Nanjing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Department of Neurology, Jiangsu Chinese Medicine Hospital, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Cardiac Surgery, The first School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Yang-Yang
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Eye Hospital, Nanjing Medical University, Nanjing, China The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China jqin710@vip.sina.com yanbiao1982@hotmail.com.
authors.forename: Qin
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Eye Hospital, Nanjing Medical University, Nanjing, China The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China jqin710@vip.sina.com yanbiao1982@hotmail.com.
authors.forename: Biao
authors.initials: B
authors.lastname: Yan
mesh_terms: D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D006801:Humans; D051379:Mice; D019636:Neurodegenerative Diseases / Q000473:pathology*; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D062085:RNA, Long Noncoding / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000473:pathology*; D015398:Signal Transduction
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C557041:MALAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding
keywords: CREB signaling; long non‐coding RNA; reactive gliosis; retinal neurodegeneration