Murine Autoimmune Optic Neuritis Is Not Phenotypically Altered by the Retinal Degeneration 8 Mutation

Invest Ophthalmol Vis Sci. 2017 Jan 1;58(1):318-328. doi: 10.1167/iovs.16-20419.

Abstract

Purpose: To investigate whether the presence of the retinal degeneration 8 (rd8) mutation in C57BL/6 mice alters the phenotype of autoimmune optic neuritis (AON).

Methods: C57BL/6J and C57BL/6N mice were genotyped for the rd8 mutation and fundus analyses and examination of retinal layer morphology were performed in vivo by scanning laser ophthalmoscopy and optical coherence tomography. Visual function was assessed by recording electroretinographs, and visual evoked potentials and retinae and optic nerves were assessed histopathologically. Retinal ganglion cell numbers were determined by retrograde labeling with fluorogold. Mice were then immunized with myelin oligodendrocyte glycoprotein 35-55 to induce AON before assessment of retinal ganglion cell degeneration, inflammatory infiltration of retinae and optic nerves, and demyelination. Furthermore, visual function was assessed by visual evoked potentials.

Results: All C57BL/6N mice were homozygous for the mutation (Crb1rd8/rd8) and had pathology typical of the rd8 mutation; however, this was not seen in the C57BL/6J (Crb1wt/wt) mice. Following induction of AON, no differences were seen between the Crb1rd8/rd8 and Crb1wt/wt mice regarding disease parameters nor regarding inner retinal degeneration either in the retina as a whole or in the inferior nasal quadrant.

Conclusions: The presence of the rd8 mutation in C57BL/6 mice does not affect the course of AON and should not provide a confounding factor in the interpretation of experimental results obtained in this model. However, it could be dangerous in other models of ocular pathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases*
  • DNA
  • DNA Mutational Analysis
  • Disease Models, Animal
  • Electroretinography
  • Evoked Potentials, Visual / physiology
  • Female
  • Genotype
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mutation*
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Optic Nerve / pathology*
  • Optic Nerve / physiopathology
  • Optic Neuritis / diagnosis
  • Optic Neuritis / genetics*
  • Optic Neuritis / immunology
  • Phenotype
  • Polymerase Chain Reaction
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / pathology*
  • Tomography, Optical Coherence / methods

Substances

  • Nerve Tissue Proteins
  • DNA