Purchase this article with an account.
Zheng Q Yin, Zui Tao, Qian Jian, Mark Gillies, Yao Chen Li; Lin28B Is Required for Initiating Maximal Müller Glia De-differentiation and Proliferation in the Regenerative Rats’ Retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):409.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The retinal regeneration and repair in higher mammalian animals are severely impeded. Although Müller cells can be activated and also show some progenitor cell characteristics under various injury and pathological condition, they form gliosis scar very soon. Unfortunately, the basic mechanisms that impede retina regeneration remain unknown. The purpose of this study was to research the molecular mechanism that impede Müller cells dedifferentiation and retina regeneration in retinitis pigmentosa.
Royal College of Surgeons rat (RCS-p+ rat) was used as the model of retinitis pigmentosa. We studied retinas from RCS rats by microscopy, flow cytometry, microRNA array, In situ Hybridization, western blot and ERG recording in vivo and vitro. Subretinal space injection was performed to overexpress the target protein in retinas.
Our present results showed that let-7 family molecules, let-7e and let-7i, were significantly overexpressed in Müller cells of degenerative retinas. As let-7 is post-transcriptionally regulated by RNA binding protein, Lin28. Herein, we provide further evidence downregulation of Lin28B is one of the key factors led to overexpression of let-7e and let-7i. Lin28B ectopic expression in Müller cells either in vivo or in vitro can suppress overexpression of let-7e and let-7i, stimulate and mobilize Müller glia de-differentiation, proliferation, promote neuronal commitment and inhibit glial fate acquisition of de-differentiated Müller cells. ERG recording revealed that the amplitudes of a-wave and b-wave were improved significantly after Lin28B delivered into subretinal space of RCS rat.
Our data uncover that downregulation of Lin28B as well as upregulation of let-7e and let-7i might be the main reason impeding Müller cells de-differentiation and proliferation in RCS rat’s retina.
This PDF is available to Subscribers Only