title: Immune priming and experimental glaucoma: the effect of prior systemic lipopolysaccharide challenge on tissue outcomes after optic nerve injury.
abstract: BACKGROUND
  Microglial activation is a prominent feature throughout the optic pathway in experimental glaucoma. Pro-inflammatory microglial activation may contribute to neurodegeneration through the release of pro-inflammatory cytokines and other inflammatory mediators. Systemic administration of lipopolysaccharide stimulates microglia to produce pro-inflammatory cytokines and chemoattractants. A preliminary investigation demonstrated pro-inflammatory microglial activation throughout the optic pathway following systemic lipopolysaccharide challenge. The aim of the current work was to investigate whether microglial priming with lipopolysaccharide would exacerbate optic nerve injury in rats following experimental glaucoma.
  
  
  METHODS
  Adult female Sprague-Dawley rats were divided into lipopolysaccharide treatment (n = 15) and saline treatment groups (n = 15). Microglial priming was induced with a 2.5-mg/kg intraperitoneal injection of lipopolysaccharide; control animals received saline. Experimental glaucoma was induced 48 h later in the right eyes of animals by laser photocoagulation of the trabecular meshwork. Animals were sacrificed 9 days after laser treatment.
  
  
  RESULTS
  The estimated number of axons per optic nerve was 51 327 ± 3868 (mean ± standard error of the mean) in the lipopolysaccharide group and 54 569 ± 6687 (mean ± standard error of the mean) in the saline group. Optic nerve axon counts were not significantly different between lipopolysaccharide and saline groups (P = 0.67).
  
  
  CONCLUSIONS
  Systemic lipopolysaccharide challenge had no discernible effect on optic nerve injury in laser-induced experimental glaucoma. These findings do not support the hypothesis that this model of experimental glaucoma involves inflammation and instead suggest that microglial activation may occur secondary to chronic neurodegeneration.
authors.affiliation: Ophthalmic Research Laboratories, South Australian Institute of Ophthalmology, Hanson Institute Centre for Neurological Diseases, Adelaide, South Australia, Australia; Department of Ophthalmology, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Narayan
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Casson
authors.forename: Andreas
authors.initials: A
authors.lastname: Ebneter
authors.forename: Glyn
authors.initials: G
authors.lastname: Chidlow
authors.forename: Peter M
authors.initials: PM
authors.lastname: Grace
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hutchinson
authors.forename: John Pm
authors.initials: JP
authors.lastname: Wood
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D002452:Cell Count; D004195:Disease Models, Animal; D005260:Female; D005901:Glaucoma / Q000378:metabolism*; D007107:Immune System / Q000187:drug effects*; D007124:Immunoenzyme Techniques; D007274:Injections, Intraperitoneal; D007429:Intraocular Pressure; D017075:Laser Coagulation; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017628:Microglia / Q000378:metabolism*; D009900:Optic Nerve / Q000473:pathology; D020221:Optic Nerve Injuries / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014129:Trabecular Meshwork / Q000601:surgery
chemical_list: D008070:Lipopolysaccharides
keywords: glaucoma; immune priming; lipopolysaccharide; microglia; retinal ganglion cell