title: Chronic intraocular pressure elevation impairs autoregulatory capacity in streptozotocin-induced diabetic rat retina.
abstract: OBJECTIVE
  To assess ocular blood flow responses to acute IOP stress following 4 weeks of chronic IOP elevation in streptozotocin (STZ)-induced diabetic and control rats. We hypothesise that chronic IOP elevation for 4 weeks will further impair blood flow regulation in STZ-induced diabetic rats eyes.
  
  
  METHODS
  Two weeks following citrate buffer or STZ-injections chronic IOP elevation was induced in Long Evans rats via fortnightly intracameral injections of microspheres (15 μm) suspended in 5% polyethylene glycol. IOP was monitored daily. Electroretinography (ERG, -6.79-2.07 log cd s m(-2) ) was undertaken at Week 4 to compare photoreceptor (RmPIII ), ON-bipolar cell (Vmax ) and ganglion cell dominant ERG [scotopic threshold response (STR)] components. 4 weeks post-chronic IOP induction, ocular blood flow (laser Doppler flowmetry) was measured in response to acute IOP challenge (10-100 mmHg, in 5 mmHg steps, each 3 min).
  
  
  RESULTS
  Four weeks of chronic IOP (mean ± S.E.M., citrate: 24.0 ± 0.3 to 30.7 ± 1.3 and STZ-diabetes: 24.2 ± 0.2 to 31.1 ± 1.2 mmHg) was associated with reduced photoreceptor amplitude in both groups (-25.3 ± 2.2% and -17.2 ± 3.0%, respectively). STZ-diabetic eyes showed reduced photoreceptor sensitivity (citrate: 0.5 ± 1.8%, STZ-diabetic: -8.1 ± 2.4%). Paradoxically ON-bipolar cell sensitivity was increased, particularly in citrate control eyes (citrate: 166.8 ± 25.9%, STZ-diabetic: 64.8 ± 18.7%). The ganglion cell dominant STR was not significantly reduced in STZ-diabetic rats. Using acute IOP elevation to probe autoregulation, we show that STZ-diabetes impaired autoregulation compared with citrate control animals. The combination of STZ-diabetes and chronic IOP elevation further impaired autoregulation.
  
  
  CONCLUSIONS
  STZ-diabetes and chronic IOP elevation appear to be additive risk factors for impairment of ocular blood flow autoregulation.
authors.affiliation: Department of Optometry and Vision Sciences, University of Melbourne, Melbourne, Australia.
authors.forename: Vickie H
authors.initials: VH
authors.lastname: Wong
authors.forename: James A
authors.initials: JA
authors.lastname: Armitage
authors.forename: Zheng
authors.initials: Z
authors.lastname: He
authors.forename: Flora
authors.initials: F
authors.lastname: Hui
authors.forename: Algis J
authors.initials: AJ
authors.lastname: Vingrys
authors.forename: Bang V
authors.initials: BV
authors.lastname: Bui
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004596:Electroretinography; D005123:Eye / Q000098:blood supply*; D007429:Intraocular Pressure / Q000502:physiology*; D008297:Male; D009798:Ocular Hypertension / Q000503:physiopathology*; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D012039:Regional Blood Flow / Q000502:physiology*; D012160:Retina / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000502:physiology; D012684:Sensory Thresholds / Q000502:physiology; D013311:Streptozocin / Q000494:pharmacology; D013312:Stress, Physiological / Q000502:physiology
chemical_list: D013311:Streptozocin
keywords: blood flow; diabetes; electroretinogram; intraocular pressure; rat; retina