Immunohistochemical evidence of inducible nitric oxide synthase and nitrotyrosine in a case of clinically isolated optic neuritis

J Neuroophthalmol. 2006 Jun;26(2):87-94. doi: 10.1097/01.wno.0000223266.48447.1b.


Background: Optic neuritis (ON) is a demyelinating inflammation of the optic nerve that may occur as an isolated disease or related to multiple sclerosis (MS). There is little evidence of whether the immunohistochemistry of ON resembles that of typical cerebral MS lesions.

Methods: Pathologic optic nerves were obtained from a patient who died of causes unrelated to ON after clinical recovery from clinically isolated ON. Normal control optic nerves were obtained from an eye bank. Normal and pathologic tissues were probed with antibodies to pathologic proteins including myelin basic protein (MBP) fragment, the inducible form of nitric oxide synthase (iNOS), macrophage markers CD14 and CD64, nitrotyrosine, and cyclooxygenase (COX-2). We also examined MBP, the oligodendrocyte marker cyclic nucleotide phosphodiesterase (CNPase), and glial fibrillary acidic protein.

Results: In the affected pathologic nerve, iNOS-positive macrophages/microglia, iNOS-positive astrocytes, COX-2, and nitrotyrosine were observed. iNOS and COX-2 were occasionally observed in the unaffected nerve. Decreased expression of MBP and CNPase was seen in the pathologic optic nerves, along with evidence of gliosis and ongoing myelin degradation indicated by the presence of MBP fragment.

Conclusions: The immunohistochemistry of clinically isolated optic neuritis, as judged by this single case, resembles that of cerebral lesions of MS in showing abnormally high levels of iNOS and nitrotyrosine as well as other mediators of immune damage.

Publication types

  • Case Reports
  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Astrocytes / enzymology
  • Astrocytes / ultrastructure
  • Biomarkers / metabolism
  • Cyclooxygenase 2 / biosynthesis
  • Disease Progression
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • Male
  • Microglia / enzymology
  • Microglia / ultrastructure
  • Myelin Basic Protein / biosynthesis
  • Nitric Oxide Synthase Type II / metabolism*
  • Optic Neuritis / enzymology*
  • Optic Neuritis / pathology
  • Prognosis
  • Tyrosine / analogs & derivatives*
  • Tyrosine / metabolism


  • Biomarkers
  • Myelin Basic Protein
  • 3-nitrotyrosine
  • Tyrosine
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2