The effect of reduced oxygen delivery and metabolism on electroretinogram b-wave in rats

Abstract

Purpose : Retinal ischemia is frequently the driving pathophysiology of vision-threatening diseases. Studies in experimental ischemia models by bilateral common carotid artery occlusion (BCCAO) have reported reduced retinal electrophysiological function. The purpose of the current study was to test the hypothesis that reduction in electroretinogram (ERG) b-wave amplitude is affected by impairments to retinal oxygen metabolism (MO₂), delivery (DO₂), and extraction fraction (OEF).

Methods : Sixteen rats underwent BCCAO or sham surgery and were evaluated at 3 or 7 days. ERG, phosphorescence lifetime imaging, and blood flow imaging were performed in both eyes. ERG b-wave amplitude was obtained at a flash intensity of 1 cd s/m². Phosphorescence lifetime images were analyzed to derive retinal arterial and venous oxygen contents (O_2A, O_2V), and arteriovenous oxygen content difference (O_2AV). Total retinal blood flow (TRBF) was calculated from retinal venous diameter and blood velocity measurements. The following equations were used: DO₂=TRBF*O_2A; MO₂=TRBF*O_2AV; OEF=MO₂/DO₂. Data from individual eyes were divided into 3 groups: sham (N=15; combined 3- and 7-days), 3-day (N=6), and 7-day (N=8) study groups. Linear mixed model analysis was used to compare sham and study groups and relate ERG data with oxygen metrics. Significance was accepted at P<0.05.

Results : ERG b-wave amplitudes in both 3-day (72±32 µV) and 7-day (100±35 µV) groups were reduced compared to the sham group (357±116 µV). In the sham group, MO₂, DO₂, and OEF were 404±119 nLO₂/min, 838±179 nLO₂/min, and 0.48 ± 0.08, respectively. Compared to the sham group, DO₂ was reduced in both the 3-day (217±50 nLO₂/min) and 7-day (270 ±52 nLO₂/min) groups. Similarly, MO₂ was reduced in both the 3-day (187±40 nLO₂/min) and 7-day (177±31 nLO₂/min) groups. OEF was increased in both the 3-day (0.87±0.11) and 7-day (0.69±0.11) groups. No significant differences were detected in b-wave amplitudes, MO₂, and DO₂ between 3- and 7-day groups; however, OEF was reduced in the 7-day group compared to the 3-day group. ERG b-wave amplitude was related to MO₂ (β=0.71 uV/nLO₂/min; P<0.001), DO₂ (β=0.35 uV/nLO₂/min; P<0.001), and OEF (β=-48.5 uV/0.1 unit; P=0.002).

Conclusions : The findings confirm our hypothesis that ERG b-wave amplitude is reduced under conditions of impaired oxygen delivery and metabolism.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.