The Gradient of Retinal Functional Changes during Acute Intraocular Pressure Elevation

Abstract

To characterize retinal function during a period of acutely elevated intraocular pressure (IOP) across a wide range of IOPs, including those typically observed in animals with experimental glaucoma. Unilateral elevation of IOP was achieved manometrically in adult Brown Norway rats (nine experimental groups; n=4-7 in each; 10-100 mmHg and sham control). Full-field ERGs were recorded simultaneously from treated and control eyes, beginning 75 minutes after IOP elevation. Scotopic ERG stimuli were brief white flashes (-6.1 to 2.7 log cd-s/m2). Photopic ERGs were recorded (1.2-2.7 log cd-s/m2) after 15 minutes of light adaptation (150 cd/m2). Relative amplitude (treated/control, %) of ERG components versus IOP was described with a cumulative normal function. Resting IOP was 12.1 +/- 2.8 mmHg and mean femoral artery pressure was 97.6 +/- 10.7 mmHg. ERG components showed a graded effect dependent on IOP. Systematic delays in the timing of the scotopic threshold response (STR) and photopic b-wave were observed between IOPs of 30 and 40 mmHg. Analysis of amplitudes revealed that the negative STR component (nSTR) and the photopic OPs were the most sensitive to acute IOP elevation. These components were first significantly affected at 50 mmHg, whereas all parameters of middle and outer retinal function (scotopic P2 and P3) remained normal. The nSTR and photopic OPs declined by 50% at IOP <61 mmHg. The scotopic P2, OPs, and positive STR (pSTR) had intermediate sensitivity, such that they were reduced by 50% at IOPs between 61 and 66 mmHg. Scotopic P2 amplitude, but not sensitivity, was significantly reduced by 60 mmHg. At 60 and 70 mm Hg, the decline in P2 amplitude was not attributable to changes in photoreceptor response (P3) amplitude or sensitivity. The least sensitive component was the scotopic a-wave (RmP3) showing a 50% reduction at an IOP of 71 mmHg. During acute IOP elevation, functional changes progress from the proximal to the distal retina. Alterations in ganglion-cell-related ERG potentials occurred at IOPs (30-50 mmHg) commonly observed in rat experimental glaucoma models. Nonspecific functional changes were observed at acute IOP above 50 mmHg, suggesting that IOP should be maintained below this level in experimental glaucoma models if selective ganglion cell injury is to be sought. Repeated IOP spikes above this level may cause permanent, nonspecific damage, perhaps via ischemic mechanisms. Thus, IOP should be monitored frequently in these models.