title: Disruption of gap junctions may be involved in impairment of autoregulation in optic nerve head blood flow of diabetic rabbits.
abstract: OBJECTIVE
  To determine whether an impairment of the autoregulatory mechanism of blood flow in the optic nerve head (ONH) is present in diabetic rabbits and whether the impairment results from the uncoupling of gap junctions.
  
  
  METHODS
  Experiments were performed on six alloxan-induced diabetic rabbits and six healthy control animals. In a test of the integrity of the autoregulatory mechanism, the intraocular pressure (IOP) was elevated from the 20-mm Hg baseline to 50 and then to 70 mm Hg. The capillary blood flow in the ONH was measured every 10 minutes by the laser speckle method, with simultaneous measurements of blood pressure. Ocular perfusion pressure (OPP) was calculated at each step, and the relationship between blood flow and OPP was analyzed. In addition, octanol, gap27 (gap junction uncouplers), or balanced saline solution was injected into the vitreous of healthy rabbits, with the balanced saline solution-injected eyes serving as the control. Changes in the ONH blood flow in response to the IOP elevation were determined in the same way.
  
  
  RESULTS
  Diabetic rabbits had a significant decrease in ONH blood flow when the OPP was reduced by an elevation of the IOP to 50 or to 70 mm Hg, whereas the ONH blood flow was well maintained in healthy rabbits. After injection of octanol (10.0 mM) or gap27 (10 μM), a reduction of OPP resulted in a significant decrease in ONH blood flow in the healthy rabbits.
  
  
  CONCLUSIONS
  These results indicate that autoregulation is disrupted in diabetic animals, and uncoupling the gap junctions in healthy rabbits also disrupts the autoregulation.
authors.affiliation: Department of Ophthalmology, Osaka Medical College, Takatsuki, Osaka, Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Shibata
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Oku
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Mami
authors.initials: M
authors.lastname: Tsujimoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Okuno
authors.forename: Tsunehiko
authors.initials: T
authors.lastname: Ikeda
mesh_terms: D020003:1-Octanol / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects; D017630:Connexins / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000503:physiopathology*; D004596:Electroretinography; D005074:Evoked Potentials, Visual; D017629:Gap Junctions / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D007429:Intraocular Pressure / Q000502:physiology; D017078:Laser-Doppler Flowmetry; D009842:Oligopeptides; D009898:Optic Disk / Q000098:blood supply*; D011817:Rabbits; D012039:Regional Blood Flow; D055351:Retinal Neurons / Q000187:drug effects / Q000502:physiology; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D017630:Connexins; D009842:Oligopeptides; D014475:Uncoupling Agents; C455880:gap 27 peptide; D020003:1-Octanol