Abstract WP165: Retinal Oxygen Metabolic, Anatomical, and Biochemical Changes in Experimental Carotid Artery Occlusion

Abstract

Purpose: Retinal ischemia has been implicated in vision-threatening diseases. Permanent bilateral common carotid artery occlusion (BCCAO) studies have reported retinal degeneration and gliosis, as well as cerebral degeneration. We hypothesized that BCCAO-induced long-term (3 to 14 days) impairments to oxygen delivery (DO 2 ), extraction fraction (OEF), and metabolism (MO 2 ) affect cellular morphology and biochemical pathways. Methods: Twenty-one rats underwent BCCAO or sham surgery. Blood flow and vascular oxygen tension imaging was performed in both eyes. Images were analyzed to derive retinal arterial and venous oxygen contents (O 2A , O 2V ), arteriovenous oxygen content difference (O 2AV ), and total retinal blood flow (TRBF). The following equations were used: DO 2 =TRBF*O 2A ; MO 2 =TRBF*O 2AV ; OEF=MO 2 /DO 2 . After imaging, immunohistochemistry and histological assays were performed on retinal sections. Results: Compared to the sham group, DO 2 was reduced in 3-day (β=-622 nLO 2 /min), 7-day (β=-614 nLO 2 /min), and 14-day (β=-605 nLO 2 /min) BCCAO groups. MO 2 was reduced in 3-day (β=-215 nLO 2 /min), 7-day (β=-256 nLO 2 /min), and 14-day (β=-262 nLO 2 /min) BCCAO groups. Compared to the sham group, OEF was increased in 3-day (β=0.405) and 7-day (β=0.209) BCCAO groups. Compared to the sham group, the thickness of the nerve fiber (β=-14.6 μm), inner nuclear (β=-7.21 μm), outer plexiform (β=-6.70 μm), and inner retina (β=-30.7 μm) layers were decreased, while thickness of the outer nuclear layer was increased (β=7.88 μm) in the 14-day BCCAO group. Gliosis was increased in the 14-day BCCAO group compared to all other groups. Compared to the sham group, TUNEL-positive cells in inner and outer nuclear layers were increased in the 3-day BCCAO group. Conclusions: The findings confirm our hypothesis that BCCAO-induced reduction in retinal DO 2 resulted in increased OEF, impairment of MO 2 , and inner retinal cell death after 3 days, whereas increased gliosis and degeneration of inner retinal cells were observed after 14 days. When compared to brain literature, the retina—an extension of the diencephalon-- showed a similar reduction in blood flow and increase in both OEF and cell-death at 3-days following BCCAO.