Alterations in inner retinal oxygen delivery and metabolism during bilateral common carotid artery occlusion in rats

Abstract

Purpose : Retinal ischemia has been identified as an important factor in the development of pathologies due to retinal diseases. Previous studies have established morphological changes in the retinal tissue following experimental ischemia induced by bilateral common carotid artery occlusion (2VO). In the current study, we report alterations in inner retinal oxygen delivery (DO₂) and metabolism (MO₂) during 2VO in rats.

Methods : The study was performed in 14 rats that were subjected to 2VO via ligation (n=5) or via clamp (n=5) or sham procedure (n=4). Multimodal imaging was performed in both eyes of each rat. Fluorescent microsphere and red-free imaging were performed to measure blood velocity and vessel diameters for calculation of total venous blood flow (BF). Phosphorescence lifetime imaging was performed to measure arterial and venous oxygen tension for calculation of arterial and venous oxygen content (O_2A, O_2V) and arteriovenous difference (O_2AV). DO₂ and MO₂ were calculated as: BF×O_2A and BF×O_2AV, respectively. Oxygen extraction fraction (OEF) was calculated as: MO₂/DO₂. The data were compared among groups using ANOVA. The relationship between oxygen metrics was determined by curve fitting.

Results : DO₂ and MO₂ of the sham eyes were 948±255 nLO₂/min and 466±103 nLO₂/min, respectively. DO₂ decreased in both ligated (175±137 nLO₂/min) and clamped (532±356 nLO₂/min) groups (P≤0.01). Similarly, MO₂ decreased in ligated (171±135 nLO₂/min) and clamped (306±135 nLO₂/min) groups (P≤ 0.05). The relationship between MO₂ and DO₂ was fit by an exponential function (R²=0.81), such that MO₂ approached an asymptote at DO₂> 500 nLO2/min and decreased with DO₂ below this threshold. OEF increased in the ligated group (0.98±0.02) compared to the sham (0.51±0.11) (P≤0.01). The relationship between OEF and DO₂ was fit by a cumulative normal distribution function (R²=0.76) with low and high asymptotes at 0.4 and 1.0, respectively.

Conclusions : Bilateral occlusion of carotid arteries resulted in a significant reduction in DO₂, though the minimal retinal blood flow was presumably due to collateral circulation. MO₂ was initially maintained with decreased DO₂ coupled with increased OEF, but eventually declined as OEF converged to a maximum value. These findings help gain a better understanding of the pathophysiology of retinal ischemic conditions.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.