title: Modeling the Chronic Loss of Optic Nerve Axons and the Effects on the Retinal Nerve Fiber Layer Structure in Primary Disorder of Myelin.
abstract: OBJECTIVE
  We determined whether the chronic lack of optic nerve myelination and subsequent axon loss is associated with optical coherence tomography (OCT) changes in the retinal nerve fiber layer (RNFL), and whether this models what occurs in multiple sclerosis (MS) and confers its use as a surrogate marker for axon degeneration.
  
  
  METHODS
  Using an animal model of Pelizaeus-Merzbacher disease (shp) bilateral longitudinal measurements of the peripapillary RNFL (spectral-domain OCT), electroretinograms (ERG), and visual evoked potentials (VEP) were performed in affected and control animals from 5 months to 2 years and in individual animals at single time points. Light and electron microscopy of the optic nerve and retina and histomorphometric measurements of the RNFL were compared to OCT data.
  
  
  RESULTS
  Of the shp animals, 17% had an average reduction of OCT RNFL thickness on the superior retinal quadrant compared to controls (P < 0.05). Electroretinograms showed normal photopic A- and B-waves but flash VEPs were disorganized in shp animals. Morphologically, the shp retinas and optic nerves revealed significant RNFL thinning (P < 0.001) without retinal ganglion cell (RGC) loss, decrease total and relative retinal axonal area, and loss of optic nerve axons. There was strong positive correlation between OCT and morphometric RNFL thickness measurements (r = 0.878, P = 0.004).
  
  
  CONCLUSIONS
  The loss of optic nerve axons demonstrated in the shp model resulted in moderate thinning of the RNFL confirmed by OCT and histology. These results indicate that OCT-derived RNFL measurement can be a useful surrogate biomarker of optic nerve axon loss and potentially disease progression in demyelinating diseases.
authors.affiliation: Department of Pathobiological Sciences School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States.
authors.forename: Leandro B C
authors.initials: LB
authors.lastname: Teixeira
authors.affiliation: Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States.
authors.forename: James N Ver
authors.initials: JN
authors.lastname: Hoeve
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Mayer
authors.affiliation: Department of Pathobiological Sciences School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Dubielzig
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States.
authors.forename: Chelsey M
authors.initials: CM
authors.lastname: Smith
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States.
authors.forename: Abigail B
authors.initials: AB
authors.lastname: Radcliff
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Duncan