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

Oncotarget. 2016 Aug 2;7(31):49368-49383. doi: 10.18632/oncotarget.10343.


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.

Keywords: Lin28B; Müller glia cell; de-differentiation; let-7.

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Dedifferentiation*
  • Cell Lineage
  • Cell Proliferation
  • Down-Regulation
  • Electroretinography
  • Ependymoglial Cells / cytology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Green Fluorescent Proteins / metabolism
  • Male
  • MicroRNAs / metabolism
  • Neuroglia / metabolism*
  • RNA-Binding Proteins / metabolism*
  • Rats
  • Retina / cytology*
  • Retinal Degeneration / metabolism
  • Stem Cells / metabolism


  • Lin28A protein, rat
  • MIRNLET7 microRNA, rat
  • MicroRNAs
  • RNA-Binding Proteins
  • Green Fluorescent Proteins