Cellular inflammation in nonarteritic anterior ischemic optic neuropathy and its primate model

Arch Ophthalmol. 2011 Dec;129(12):1583-91. doi: 10.1001/archophthalmol.2011.351.

Abstract

Objective: To correlate potential inflammatory responses in nonarteritic anterior ischemic optic neuropathy (NAION) with a lesion possessing many physiologic and histologic similarities from a model of nonhuman primate NAION (pNAION).

Methods: Using immunohistochemistry and confocal microscopic analysis, we evaluated the relative numbers of inflammatory cell types in the single available clinical specimen of early NAION (21 days after event). We correlated this with the temporal inflammatory response occurring in optic nerve tissue at different times following pNAION induction.

Results: In pNAION, there is a previously unsuspected infiltration of polymorphonuclear leukocytes occurring almost immediately after infarct induction, followed by invasion of ED1+ extrinsic macrophages, which peaks 5 weeks after infarct. Intrinsic microglia accumulate up to 70 days after induction in the area of primary axonal loss. The analyzed human NAION specimen was similar to 21-day pNAION tissue, with extrinsic macrophages and intrinsic microglial cells in the region of focal axon loss.

Conclusions: Cellular inflammation plays a major early role following white-matter (optic nerve) infarct, with both polymorphonuclear leukocyte and macrophage function involved in debris elimination and tissue remodeling. The optic nerve in NAION and its primate model are associated with early cellular inflammation, previously unsuspected, that may contribute to postinfarct optic nerve damage.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Axons / metabolism
  • Axons / pathology
  • Biomarkers / metabolism
  • Calcium-Binding Proteins
  • Cell Count
  • Cross-Sectional Studies
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal*
  • Fluorescent Antibody Technique, Indirect
  • Giant Cell Arteritis / immunology
  • Giant Cell Arteritis / pathology
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology
  • Macaca mulatta
  • Macrophages / metabolism
  • Macrophages / pathology*
  • Male
  • Microfilament Proteins
  • Microscopy, Confocal
  • Neutrophils / metabolism
  • Neutrophils / pathology*
  • Optic Nerve / metabolism
  • Optic Nerve / pathology*
  • Optic Neuritis / immunology*
  • Optic Neuritis / pathology
  • Optic Neuropathy, Ischemic / immunology*
  • Optic Neuropathy, Ischemic / pathology
  • Rose Bengal / toxicity

Substances

  • AIF1 protein, human
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers
  • CD68 antigen, human
  • Calcium-Binding Proteins
  • DNA-Binding Proteins
  • Microfilament Proteins
  • Rose Bengal