Abstract
Purpose:
To consider if chronic hypertension protects against chronic intraocular pressure elevation in rats.
Methods:
Anesthetised (60:5mg/kg ketamine:xylazine) adult Long-Evans rats were implanted with Alzet osmotic minipumps (2ML4). The hypertensive group (n=8) received subcutaneous infusion of 150ng/kg/min angiotensin II and the normotensive group (n=8) received saline. Four weeks after pump implantation, animals were anesthetised and one randomly selected eye underwent unilateral circumlimbal suture (7/0) to chronically increase IOP. The contralateral eye was left as an untreated control. Systolic blood pressure (SBP) and IOP were measured weekly in awake animals with tail cuff sphygmomanometer and TonoLab, to return ocular perfusion pressure (OPP). Electroretinography and SD-OCT were measured under anesthetisia at baseline, week 4 (before suture application), week 9 and 12. ERG waveforms were analysed to return measures of photoreceptor (a-wave), bipolar cell (b-wave) and RGC (scotopic threshold response, STR) activity. Amplitudes were expressed relative (average%±SEM) to control eyes. OCT images returned retinal ganglion cell complex (GCC), retinal nerve fibre layer (RNFL) and retinal thickness.
Results:
SBP was significantly increased in hypertensive rats (160±5mmHg vs 123±2mmHg). Suture application produced IOP elevation in normotensive (over 8 weeks 21.9±0.6 vs 12.9±0.2 mmHg [OPP 102±3 vs 116±2 mmHg]) and hypertensive rats (24.9±1.1 vs 13.3±0.2 mmHg, [OPP 139±4 vs 151±4mmHg]). Systemic hypertension did not alter functional outcomes. IOP elevation produced similar reductions in the a-wave and b-wave in both hypertensive (-5.4±2.0%; -7.0±2.8%) and normotensive rats (-14.7±3.5%; -12.0±2.8%). There was significantly greater attenuation of the STR compared with the a-wave and b-wave (hypertensive -32.1±7.4%; normotensive -27.5±6%). In hypertensive and normotensive rats, by week 12 there was a significant reduction in RNFL thickness (-16.8±2.9%, -18.2±3.6%) with little change in GCC (2.8±1.3%, -1.7±1.6%) or retinal (4.2±1%, 2.1±0.8%) thickness.
Conclusions:
Despite the significantly increased OPP secondary to systemic hypertension, retinal function and RNFL thickness were not protected against chronic IOP elevation. This differs from past findings where acute high BP was protective, which indicates that the chronicity of the hypertension may negate the protective effect afforded by improved OPP.