title: Elevated intraocular pressure causes inner retinal dysfunction before cell loss in a mouse model of experimental glaucoma.
abstract: OBJECTIVE
  We assessed the relationship among intraocular pressure (IOP), histology, and retinal function changes in a mouse model of induced, chronic, mild ocular hypertension.
  
  
  METHODS
  IOP was elevated experimentally via anterior chamber injection of polystyrene beads and measured twice weekly with a rebound tonometer. Histology was assessed with a combination of neurobiotin (NB) retrograde labeling of retinal ganglion cells (RGCs) and TO-PRO3 staining. Retinal function was assessed with serial dark-adapted electroretinograms (ERGs) optimized for detection of the a-wave, b-wave, and positive and negative scotopic threshold responses (pSTR, nSTR). Comparisons between bead-injected and saline-injected (control) eyes were conducted.
  
  
  RESULTS
  IOP remained elevated for at least 3 months following a single injection of polystyrene beads. Elevated IOP resulted in a mild, progressive reduction of RGCs, and a mild increase in axial length at 6 and 12 weeks after bead injection. The raw b-wave amplitude was increased shortly after IOP elevation, but the raw a-wave, pSTR, and nSTR amplitudes were unchanged. pSTR and nSTR amplitudes were normalized to the increased b-wave. With this normalization, the pSTR amplitude was decreased shortly after IOP elevation.
  
  
  CONCLUSIONS
  Polystyrene bead injection results in a mild, chronic elevation of IOP that recapitulates several critical aspects of human ocular hypertension and glaucoma, and results in early changes in retinal electrical function that precede histologic changes. It is possible that glaucoma associated with elevated IOP involves the early disruption of a complex combination of retinal synapses.
authors.affiliation: Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas 77030, USA. benjamin.frankfort@bcm.edu
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Frankfort
authors.forename: A Kareem
authors.initials: AK
authors.lastname: Khan
authors.forename: Dennis Y
authors.initials: DY
authors.lastname: Tse
authors.forename: Inyoung
authors.initials: I
authors.lastname: Chung
authors.forename: Ji-Jie
authors.initials: JJ
authors.lastname: Pang
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Yang
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Gross
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Wu
mesh_terms: D000818:Animals; D058452:Axial Length, Eye; D015415:Biomarkers / Q000378:metabolism; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death; D003623:Dark Adaptation; D004195:Disease Models, Animal; D004596:Electroretinography; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D007150:Immunohistochemistry; D007429:Intraocular Pressure / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009798:Ocular Hypertension / Q000378:metabolism / Q000503:physiopathology*; D012164:Retinal Diseases / Q000378:metabolism / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*; D014065:Tonometry, Ocular
chemical_list: D015415:Biomarkers; C070614:neurobiotin; D001710:Biotin