title: Radiation pretreatment does not protect the rat optic nerve from elevated intraocular pressure-induced injury.
abstract: OBJECTIVE
  Optic nerve injury has been found to be dramatically reduced in a genetic mouse glaucoma model following exposure to sublethal, head-only irradiation. In this study, the same radiation treatment was used prior to experimental induction of elevated intraocular pressure (IOP) to determine if radiation is neuroprotective in another glaucoma model.
  
  
  METHODS
  Episcleral vein injection of hypertonic saline was used to elevate IOP unilaterally in two groups of rats: (1) otherwise untreated and (2) radiation pretreated, n > 25/group. Intraocular pressure histories were collected for 5 weeks, when optic nerves were prepared and graded for injury. Statistical analyses were used to compare IOP history and nerve injury. The density of microglia and macrophages in two nerve head regions was determined by Iba1 immunolabeling.
  
  
  RESULTS
  Mean and peak IOP elevations were not different between the two glaucoma model groups. Mean optic nerve injury grades were not different in glaucoma model optic nerves and were equivalent to approximately 35% of axons degenerating. Nerves selected for lower mean or peak IOP elevations did not differ in optic nerve injury. Similarly, nerves selected for lower injury grade did not differ in IOP exposure. By multiple regression modeling, nerve injury grade was most significantly associated with mean IOP (P < 0.002). There was no significant effect of radiation treatment. Iba1+ cell density was not altered by radiation treatment.
  
  
  CONCLUSIONS
  In contrast to previous observations in a mouse genetic glaucoma model, head-only irradiation offers the adult rat optic nerve no protection from optic nerve degeneration due to chronic, experimentally induced IOP elevation.
authors.affiliation: The Kenneth C. Swan Ocular Neurobiology Laboratory, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Johnson
authors.affiliation: The Kenneth C. Swan Ocular Neurobiology Laboratory, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: William O
authors.initials: WO
authors.lastname: Cepurna
authors.affiliation: The Kenneth C. Swan Ocular Neurobiology Laboratory, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States Public Health & Preventive Medicine, Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: Dongseok
authors.initials: D
authors.lastname: Choi
authors.affiliation: The Kenneth C. Swan Ocular Neurobiology Laboratory, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: Tiffany E
authors.initials: TE
authors.lastname: Choe
authors.affiliation: The Kenneth C. Swan Ocular Neurobiology Laboratory, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: John C
authors.initials: JC
authors.lastname: Morrison
mesh_terms: D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D005901:Glaucoma / Q000150:complications / Q000503:physiopathology / Q000532:radiotherapy*; D007429:Intraocular Pressure / Q000502:physiology*; D008297:Male; D009900:Optic Nerve / Q000473:pathology / Q000528:radiation effects*; D009901:Optic Nerve Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D011914:Rats, Inbred BN; D012165:Retinal Ganglion Cells / Q000473:pathology / Q000528:radiation effects; D014065:Tonometry, Ocular
keywords: animal models; axon degeneration; glaucoma; intraocular pressure; optic nerve; radiation