Alterations in retinal oxygen metrics, thickness, function, and ganglion cell counts after experimental ocular hypertension-induced ischemia/reperfusion injury

Abstract

Purpose : Transient elevation of intraocular pressure (IOP) causes both mechanical and ischemic damage to the optic nerve and retina tissues. The purpose of the study was to test the hypothesis that retinal oxygen metrics are impaired and associated with visual dysfunction, retinal thinning, and retinal ganglion cell (RGC) loss after ischemia/reperfusion injury induced by ocular hypertension.

Methods : Right (study) eyes of 10 rats were subjected to anterior chamber cannulation to elevate the IOP for 90 minutes, followed by 7 days of reperfusion. Fellow eyes served as normal controls. Pattern-evoked electroretinography (PERG) and optical coherence tomography (OCT) were performed to measure RGC function and total retinal thickness (TRT), respectively. Retinal arterial and venous oxygen contents (O_2A and O_2V) were measured using phosphorescence lifetime imaging. Fluorescence and red-free imaging were performed to quantify total retinal blood flow (TRBF). Retinal oxygen delivery (DO₂), metabolism (MO₂), and extraction fraction (OEF) were calculated. RGCs were counted from immunofluorescence-stained retina whole-mounts. Individual retinal layers thicknesses were measured from retinal histology sections.

Results : During ischemia, IOP measurements were 15.7±0.5mmHg and 88.6±6.6mmHg in control and study eyes, respectively (p<0.0001). The PERG amplitudes were 5.2±1.5µV and 1.4±0.35µV in control and study eyes, respectively (p<0.0001). TRT was 251±7μm and 166±23μm in control and study eyes, respectively (p≤0.0001). TRBF was 6.6±1.0µL/min and 4.0±0.8µL/min in control and study eyes, respectively (p<0.0003). DO2 was 912±183nLO2/min and 574±142nLO2/min in control and study eyes, respectively (p=0.001). MO2 was 368±81nLO2/min and 222±65nLO2/min in control and study eyes, respectively (p=0.003). OEF did not differ significantly between eyes (p=0.70). The number of RGCs was 61±23) and 35±12 in control and study eyes, respectively (p=0.01). Decreased DO2 and MO2 were correlated with decreased PERG amplitude (r≥0.6, p≤0.005) and decreased TRT (r=0.7, p≤0.002). Decreased RGCs counts were correlated with decreased TRT (r=0.6, p=0.04).

Conclusions : Impairments in retinal oxygen delivery and metabolism and their correlations with visual dysfunction and cell loss were reported for the first time in an experimental ischemia/reperfusion model of glaucoma.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.