title: Evaluation of retinal nerve fiber layer thickness and axonal transport 1 and 2 weeks after 8 hours of acute intraocular pressure elevation in rats.
abstract: OBJECTIVE
  To compare in vivo retinal nerve fiber layer thickness (RNFLT) and axonal transport at 1 and 2 weeks after an 8-hour acute IOP elevation in rats.
  
  
  METHODS
  Forty-seven adult male Brown Norway rats were used. Procedures were performed under anesthesia. The IOP was manometrically elevated to 50 mm Hg or held at 15 mm Hg (sham) for 8 hours unilaterally. The RNFLT was measured by spectral-domain optical coherence tomography. Anterograde and retrograde axonal transport was assessed from confocal scanning laser ophthalmoscopy imaging 24 hours after bilateral injections of 2 μL 1% cholera toxin B-subunit conjugated to AlexaFluor 488 into the vitreous or superior colliculi, respectively. Retinal ganglion cell (RGC) and microglial densities were determined using antibodies against Brn3a and Iba-1.
  
  
  RESULTS
  The RNFLT in experimental eyes increased from baseline by 11% at 1 day (P < 0.001), peaked at 19% at 1 week (P < 0.0001), remained 11% thicker at 2 weeks (P < 0.001), recovered at 3 weeks (P > 0.05), and showed no sign of thinning at 6 weeks (P > 0.05). There was no disruption of anterograde transport at 1 week (superior colliculi fluorescence intensity, 75.3 ± 7.9 arbitrary units [AU] for the experimental eyes and 77.1 ± 6.7 AU for the control eyes) (P = 0.438) or 2 weeks (P = 0.188). There was no obstruction of retrograde transport at 1 week (RCG density, 1651 ± 153 per mm(2) for the experimental eyes and 1615 ± 135 per mm(2) for the control eyes) (P = 0.63) or 2 weeks (P = 0.25). There was no loss of Brn3a-positive RGC density at 6 weeks (P = 0.74) and no increase in microglial density (P = 0.92).
  
  
  CONCLUSIONS
  Acute IOP elevation to 50 mm Hg for 8 hours does not cause a persisting axonal transport deficit at 1 or 2 weeks or a detectable RNFLT or RGC loss by 6 weeks but does lead to transient RNFL thickening that resolves by 3 weeks.
authors.affiliation: Discoveries in Sight Research Laboratories, Legacy Good Samaritan Devers Eye Institute, and Legacy Research Institute, Legacy Health, Portland, Oregon.
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Abbott
authors.forename: Tiffany E
authors.initials: TE
authors.lastname: Choe
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Lusardi
authors.forename: Claude F
authors.initials: CF
authors.lastname: Burgoyne
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Brad
authors.initials: B
authors.lastname: Fortune
mesh_terms: D000208:Acute Disease; D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D001369:Axons / Q000473:pathology*; D002452:Cell Count; D005456:Fluorescent Dyes / Q000378:metabolism; D005464:Fluorobenzenes / Q000378:metabolism; D007429:Intraocular Pressure; D008297:Male; D017628:Microglia / Q000166:cytology; D009798:Ocular Hypertension / Q000503:physiopathology*; D009887:Ophthalmoscopy; D009901:Optic Nerve Diseases / Q000503:physiopathology*; D051381:Rats; D011914:Rats, Inbred BN; D012165:Retinal Ganglion Cells / Q000473:pathology*; D055351:Retinal Neurons / Q000502:physiology; D013997:Time Factors; D041623:Tomography, Optical Coherence; D014065:Tonometry, Ocular
chemical_list: C513915:AlexaFluor 488 carboxylic acid tetrafluorophenyl ester; D005456:Fluorescent Dyes; D005464:Fluorobenzenes
keywords: axonal transport; confocal scanning laser ophthalmoscope; glaucoma; optical coherence tomography; retinal ganglion cell; retinal nerve fiber layer