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

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.

Activation of liver X receptor delayed the retinal degeneration of rd1 mice through modulation of the immunological function of glia

“…Western blot analysis was performed according to our previous methods [ 43 ]. After eyes were enucleated from sacrificed mice, the retinas were isolated from the globe and mixed in ice-cold tissue lysis buffer (1% PSMF + 99% RIPA).…”

“…Visual electrophysiological tests were performed as described previously [ 41 , 43 ]. Before the test, mice at P14 were dark-adapted for nearly 12 h. Intramuscular injections of amine (100 mg/kg) and xylazine (12 mg/kg) were performed for anesthesia.…”

Synergistic neuroprotective effect of rasagiline and idebenone against retinal ischemia-reperfusion injury via the Lin28-let-7-Dicer pathway

“…These events cause an increase in mature microRNA levels in neurons and result in cellular repair [ 15 – 17 ]. The work by Tao and his colleagues suggested that the Lin28-let-7-Dicer pathway plays a critical role in retinal neurogenesis and regeneration [ 18 , 19 ].…”

Endogenous Mobilization of Bone-Marrow Cells Into the Murine Retina Induces Fusion-Mediated Reprogramming of Müller Glia Cells

“…In particular, proliferation of murine MGCs can be stimulated by overexpression of Ascl1, a transcription factor essential during retinal development ( Pollak et al, 2013 ). Pharmacological perturbation of specific signaling pathways can also stimulate the neural regenerative potential of mammalian MGCs; these include, for instance, Wnt/β-catenin, EGF, FGF, and insulin pathways ( Karl et al, 2008 ; Osakada et al, 2007 ; Close et al, 2006 ; Todd et al, 2015 ; Ooto et al, 2004 ; Tao et al, 2016 ; Yao et al, 2016 ).…”