Abstract
Purpose: :
We consider whether diabetes renders retinal function susceptible to chronic intraocular pressure (IOP) elevation. We also consider whether diabetes and chronic IOP renders ocular blood flow (OBF) more sensitive to acute IOP stress.
Methods: :
Baseline scotopic electroretinogram (-6.79 - 2.07 log cd.s.m-2) responses were measured in anaesthetised (60:5 mg/kg Ket:Xyl) dark-adapted (>12 hours) Long-Evans rats (age: 5 weeks) 2 weeks following citrate buffer (c, control) and streptozotocin injections (STZ, 65 mg/kg) to elevate blood glucose to >15 mmol/L. Two weeks later chronic IOP elevation was maintained over 4 weeks via fortnightly anterior chamber injections of 15µm microsphere suspended in 5% polyethylene glycol. IOP was measured in awake rats daily before and after chronic IOP induction (mean±SEM). Weekly functional assays were conducted thereafter (expressed relative to control baseline, %). Four weeks after IOP elevation, OBF (laser Doppler flowmetry) was measured in response to acute IOP challenge (10-100 mmHg, 3mins/5 mmHg). This was compared with IOP-OBF profile measured from STZ rats without chronic IOP elevation. Data are expressed relative to baseline (%, 10 mmHg).
Results: :
Microsphere injections increased IOP from 24.0±0.3 to 30.7±1.3 and from 24.2±0.2 to 31.1±1.2 for control (n=7) and STZ (n=9) rats, respectively. Systolic blood pressures were similar (c: 108±5, STZ: 119±7 mmHg, P=0.17). Chronic IOP elevation affected diabetic retinal function more than controls for photoreceptor amplitude (c: -25.3±2.2, STZ: -17.2±3.0%; P=0.014), photoreceptor sensitivity (c: 0.5±1.8, STZ: -8.1±2.4%, P<0.05) and ON-bipolar cell sensitivity (c: 166.8±25.9, STZ: 64.8±18.7%, P<0.05). Ganglion cell function was 20.4±7.8% worse in diabetes than controls (P=0.025). Diabetes increased the susceptibility of OBF to acute IOP insult by ~10 mmHg (50% response, c [n=7]: 53.4, STZ [n=10]: 43.9 mmHg) when compared with controls. Chronic IOP overlay in STZ animals further increased OBF susceptibility to acute IOP challenge by a further ~8 mmHg (n=5, 50% response, ~30 mmHg). This effect was not seen from healthy animals.
Conclusions: :
STZ-diabetes increases the susceptibility of retinal function to chronic IOP stress. Diabetes increases OBF response to acute IOP challenge, an effect exacerbated by chronic IOP overlay, suggesting impaired capacity to maintain normal retinal function under duress.
Keywords: diabetes • intraocular pressure • blood supply