Oncotarget

Research Papers:

Lin28B promotes Müller glial cell de-differentiation and proliferation in the regenerative rat retinas

Zui Tao, Chen Zhao, Qian Jian, Mark Gillies, Haiwei Xu and Zheng Qin Yin _

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Oncotarget. 2016; 7:49368-49383. https://doi.org/10.18632/oncotarget.10343

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Abstract

Zui Tao1,2, Chen Zhao1,2, Qian Jian1,2, Mark Gillies3, Haiwei Xu1,2, Zheng Qin Yin1,2

1Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China

2Key Laboratory of Visual Damage and Regeneration and Restoration of Chongqing, Chongqing, 400038, China

3Save Sight Institute, South Block, Sydney Eye Hospital, Sydney, NSW, 2001, Australia

Correspondence to:

Zheng Qin Yin, email: qinzyin@aliyun.com

Haiwei Xu, email: haiweixu2001@163.com

Keywords: Müller glia cell, de-differentiation, Lin28B, let-7

Received: March 18, 2016     Accepted: June 13, 2016     Published: June 30, 2016

ABSTRACT

Retinal regeneration and repair are severely impeded in higher mammalian animals. Although Müller cells can be activated and show some characteristics of progenitor cells when injured or under pathological conditions, they quickly form gliosis scars. Unfortunately, the basic mechanisms that impede retinal regeneration remain unknown. We studied retinas from Royal College of Surgeon (RCS) rats and found that let-7 family molecules, let-7e and let-7i, were significantly overexpressed in Müller cells of degenerative retinas. It demonstrated that down-regulation of the RNA binding protein Lin28B was one of the key factors leading to the overexpression of let-7e and let-7i. Lin28B ectopic expression in the Müller cells suppressed overexpression of let-7e and let-7i, stimulated and mobilized Müller glia de-differentiation, proliferation, promoted neuronal commitment, and inhibited glial fate acquisition of de-differentiated Müller cells. ERG recordings revealed that the amplitudes of a-wave and b-wave were improved significantly after Lin28B was delivered into the subretinal space of RCS rats. In summary, down-regulation of Lin28B as well as up-regulation of let-7e and let-7i may be the main factors that impede Müller cell de-differentiation and proliferation in the retina of RCS rats.


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