Chronic intraocular pressure elevation impairs autoregulatory capacity in streptozotocin-induced diabetic rat retina

PurposeTo assess ocular blood flow responses to acute IOP stress following 4weeks of chronic IOP elevation in streptozotocin (STZ)-induced diabetic and control rats. We hypothesise that chronic IOP elevation for 4weeks will further impair blood flow regulation in STZ-induced diabetic rats eyes. MethodsTwo weeks following citrate buffer or STZ-injections chronic IOP elevation was induced in Long Evans rats via fortnightly intracameral injections of microspheres (15m) suspended in 5% polyethylene glycol. IOP was monitored daily. Electroretinography (ERG, -6.79-2.07 log cdsm(-2)) was undertaken at Week 4 to compare photoreceptor (Rm(PIII)), ON-bipolar cell (V-max) and ganglion cell dominant ERG [scotopic threshold response (STR)] components. 4weeks post-chronic IOP induction, ocular blood flow (laser Doppler flowmetry) was measured in response to acute IOP challenge (10-100mmHg, in 5mmHg steps, each 3min). ResultsFour weeks of chronic IOP (meanS.E.M., citrate: 24.0 +/- 0.3 to 30.7 +/- 1.3 and STZ-diabetes: 24.2 +/- 0.2 to 31.1 +/- 1.2mmHg) 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. ConclusionsSTZ-diabetes and chronic IOP elevation appear to be additive risk factors for impairment of ocular blood flow autoregulation.