The Rate of Inner and Outer Retinal Recovery from Acute IOP Elevation

Abstract

Purpose: : To characterize the rate of functional recovery in inner and outer retinal responses challenged by intraocular pressure (IOP) spikes.

Methods: : IOP was elevated in anesthetized (Ketamine:Xylazine, 60:5 mg/kg) dark–adapted Long–Evans rats by raising a saline reservoir to calibrated heights above the eye. IOP spikes were achieved by maintaining IOP at 50 (42 min, n = 7) and 70 mmHg (15, 30 and 60 min, n = 6/group). Following cannulation and re–adaptation, baseline ERGs were recorded to dim (average 20 flashes, –4.8 log cd.s.m^–2) and bright (single flash, 1.0 log cd.s.m^–2) stimuli prior to IOP elevation. Electroretinogram (ERG) responses were recorded at 5 minute intervals during and following IOP elevation. Dim flashes were analyzed in terms of the negative Scotopic Threshold Response (nSTR). Bright ERGs were analyzed in terms of photoreceptoral P3 and post–receptoral P2 (raw–P3). Data are expressed relative to baseline and analyzed using t–test. Rate of recovery was quantified by fitting a logistic function and recovery time constants were compared using a non–parametric bootstrap.

Results: : IOP spikes produced a greater loss of inner retinal responses. Comparison of IOP spikes with common exposure (IOP magnitude * time, IOP₅₀ x 42 min versus IOP₇₀ x 30 min), revealed that higher IOP caused a significantly (p<0.05) greater functional deficit in the P3 (IOP₅₀: –12 ± 5%, vs IOP₇₀: –21 ± 7%), P2 (IOP₅₀: –31 ± 11%, IOP₇₀: –99 ± 3%) and nSTR (IOP₅₀: –73 ± 7% vs IOP₇₀: –94 ± 2%). Higher IOP also resulted in slower nSTR recovery, with recovery time constants for IOP₇₀ of 31 min (CL_2.5%, 28; CL_97.5%, 39 min) and IOP₅₀ of 22 min (CL_2.5%, 15; CL_97.5%, 41 min). Varying exposure with a fixed IOP (70 mmHg) resulted in slower recovery for progressively longer durations: 15 min (t_c = 13; CL_2.5%, 11; CL_97.5%, 16 min), 30 min (t_c = 31; CL_2.5%, 28; CL_97.5%, 39 min) and 60 min (t_c = 60; CL_2.5%, 50; CL_97.5%, 64 min).

Conclusions: : ERG components arising form the inner retina are more affected by IOP spikes than those arising from the outer retina. For a fixed IOP magnitude of varying exposure the rate of recovery is linearly related to spike duration. The IOP magnitude (50 versus 70 mmHg) is an independent variable in the rate of recovery.

Keywords: electroretinography: non-clinical • intraocular pressure • ganglion cells