title: Noninvasive assessments of optic nerve neurodegeneration in transgenic mice with isolated optic neuritis.
abstract: OBJECTIVE
  To determine if phosphorylated neurofilament heavy chain (pNF-H) released into the bloodstream and the pattern ERG are noninvasive indicators of neurodegeneration in experimental optic neuritis.
  
  
  METHODS
  Serum from Myelin oligodendrocyte glycoprotein (MOG)-specific T cell receptor-positive (TCR+) transgenic mice that develop isolated optic neuritis usually without any other characteristic lesions of inflammation or demyelination in the spinal cord and littermates negative for the transgene were assayed for the presence of serum phosphorylated neurofilament H (pNF-H). In vivo measurements of optic nerve and retinal ganglion cell injury were assessed by magnetic resonance imaging (MRI), optical coherence tomography (OCT), and pattern electroretinogram (PERG). Automated two dimensional fluorescence differential in-gel electrophoresis (2D-DIGE) of pooled optic nerve samples, light, and transmission electron micrographs were used to evaluate optic atrophy postmortem.
  
  
  RESULTS
  We found an almost 3-fold elevation in serum pNF-H levels in MOG+ mice relative to MOG-littermates (P = 0.02). 2D-DIGE revealed a 3-fold reduction in optic nerve neurofilaments. Visual function assessed by the PERG was reduced by one-quarter (P = 0.033) and latencies increased by 38% (P = 0.036). MOG+ mice with the lowest PERG amplitudes had optic nerve atrophy visualized by MRI. Optic nerve diameters were reduced by one-third (P = 0.0001) and axon counts reduced by more than two-thirds. Histopathology of the spinal cords was normal.
  
  
  CONCLUSIONS
  Elevated serum pNF-H levels and the PERG are useful markers of neurodegeneration of the optic nerve in isolated experimental optic neuritis. Our findings suggest that elevations of this axonal protein in patients with optic neuritis who had a poor visual outcome are likely also due to demise of optic nerve axons.
authors.affiliation: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Venu
authors.initials: V
authors.lastname: Talla
authors.forename: Cui
authors.initials: C
authors.lastname: Yang
authors.forename: Gerry
authors.initials: G
authors.lastname: Shaw
authors.forename: Vittorio
authors.initials: V
authors.lastname: Porciatti
authors.forename: Rajeshwari D
authors.initials: RD
authors.lastname: Koilkonda
authors.forename: John
authors.initials: J
authors.lastname: Guy
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004596:Electroretinography; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000175:diagnosis* / Q000503:physiopathology; D016900:Neurofilament Proteins / Q000097:blood*; D009900:Optic Nerve; D009902:Optic Neuritis / Q000175:diagnosis* / Q000503:physiopathology; D012165:Retinal Ganglion Cells / Q000502:physiology
chemical_list: D016900:Neurofilament Proteins; C051774:neurofilament protein H
keywords: axonal degeneration; neurodegeneration; neurofilaments; neuroophthalmology; optic neuritis