RERE deficiency causes retinal and optic nerve atrophy through degeneration of retinal cells

Dev Dyn. 2021 Oct;250(10):1398-1409. doi: 10.1002/dvdy.330. Epub 2021 Mar 29.

Abstract

Background: The arginine-glutamic acid dipeptide repeats gene (RERE) encodes a nuclear receptor coregulator that modulates gene expression through its interaction with transcriptional machinery. In humans, RERE deficiency causes neurodevelopmental disorder with or without structural defects of the brain, eye, heart, and kidney (NEDBEH). Ophthalmological defects are seen in approximately one third of individuals with NEDBEH and in RERE-deficient mice which can serve as a useful animal model.

Results: In mice, RERE is expressed in a subset of retinal ganglion cells (RGC), the lens epithelium, and the ciliary body during the embryonic period. RERE expression expands into the outer nuclear layer and the inner nuclear layer during the postnatal period. RERE-deficient mice have retinal and optic nerve atrophy. We show that RERE deficiency causes progressive loss of retinal cells and apoptosis of retinal cells in the ganglion cell layer as early as E17.5. The number of RGCs is also reduced in RERE-deficient embryos and mice.

Conclusions: We conclude that RERE is required to control the apoptosis of retinal cells in the developing retina, and that RERE deficiency results in the retina atrophy through degeneration of the retinal cells and optic nerve atrophy through the loss of RGCs.

Keywords: NEDBEH; RERE; optic nerve atrophy; retinal degeneration; retinal ganglion cells.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Atrophy / genetics
  • Atrophy / metabolism
  • Atrophy / pathology
  • Disease Models, Animal
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Optic Nerve / metabolism*
  • Optic Nerve / pathology
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Retina / metabolism*
  • Retina / pathology
  • Retinal Degeneration / genetics
  • Retinal Degeneration / metabolism*
  • Retinal Degeneration / pathology

Substances

  • Nerve Tissue Proteins
  • Repressor Proteins
  • atrophin 2, mouse