Effects of Ischemia and Reperfusion on Retinal Oxygen Delivery, Metabolism, Extraction Fraction, and Function after Ophthalmic Vessel Occlusion in Rats

Abstract

Purpose : Retinal ischemia is in many diseases that cause visual impairment and blindness. Under ophthalmic vessel occlusion (OVO), after ischemia durations greater than 60 minutes, studies have reported reductions in retinal oxygen metabolism (MO₂) and delivery (DO₂), increased extraction fraction (OEF), electrophysiological dysfunction and histological damage. However, there is no information on these oxygen parameters under variable ischemia and reperfusion durations. We hypothesized that after ischemia durations greater than 60 minutes, MO₂, DO₂, OEF, and electrophysiological function outcomes improve with duration of reperfusion.

Methods : Fifty-three rats underwent unilateral OVO (N=45) or sham surgery (N=8) and were evaluated after 2 reperfusion durations. After 60-min reperfusion, groups with ischemia durations of 60-min (N=7), 90-min (N=5), 120-min (N=10), and 150-min (N=3) were evaluated. After 7-days of reperfusion, groups with ischemia durations of 60-min (N=6), 90-min (N=4), 120-min (N=6), and 180-min (N=4) were evaluated. Phosphorescence lifetime and blood flow imaging, and electroretinography (ERG) were performed. Images were analyzed to derive MO₂, DO₂, and OEF. ERG b-wave amplitude was measured after 7-days of reperfusion (N=15). Data in OVO and sham groups were compared, and MO₂ was related to ERG data.

Results : In the sham group, MO₂, DO₂, and OEF were 378±90 nLO₂/min, 709±163 nLO₂/min, and 0.53±0.07, respectively. After 60-min reperfusion, MO₂ was lower in 90- (73±53 nLO₂/min), 120- (162±102 nLO₂/min), and 150-min (110±150 nLO₂/min) groups (P≤0.01). OEF was lower in 90- (0.13±0.10), 120- (0.24±0.15), and 150-min (0.21±0.13) groups (P<0.01). After 7-days reperfusion, MO₂ was lower in the 180-min (161±138 nLO₂/min) group (P=0.04). OEF was lower in the 180-min group (0.27±0.16) (P=0.01). At both reperfusion durations, DO₂ was not different in OVO groups compared to sham (P>0.19). In the sham group, ERG b-wave amplitude was 464±163 µV. ERG b-wave amplitude was lower in 120- (126±117 µV) and 180-min (42.1±19.3 µV) groups (P≤0.002). MO₂ was directly associated with ERG b-wave amplitude (r=0.61; P=0.02; N=15).

Conclusions : With ischemia durations of 90- and 120-min, reductions in MO₂ and OEF were observed after reperfusion durations of 60 minutes, but not 7-days, indicating better outcomes after longer reperfusion durations.

This is a 2020 ARVO Annual Meeting abstract.