Relation of Retinal Oxygen Measures to Electrophysiology and Survival Indicators after Permanent, Incomplete Ischemia in
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ORIGINAL ARTICLE
Relation of Retinal Oxygen Measures to Electrophysiology and Survival Indicators after Permanent, Incomplete Ischemia in Rats Nathanael Matei 1 & Sophie Leahy 1 & Selin Auvazian 1 & Biju Thomas 1 & Norman P. Blair 2 & Mahnaz Shahidi 1 Received: 29 October 2019 / Revised: 21 February 2020 / Accepted: 27 February 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Studies in experimental ischemia models by permanent bilateral common carotid artery occlusion (BCCAO) have reported reduced retinal electrophysiological function, coupled with inner retinal degeneration and gliosis. In the current study, we tested the hypothesis that long-term (up to 14 days) BCCAO impairs oxygen delivery (DO2), which affects oxygen metabolism (MO2) and extraction fraction (OEF), electrophysiological function, morphology, and biochemical pathways. Twenty-one rats underwent BCCAO (N = 12) or sham surgery (N = 9) and were evaluated in separate groups after 3, 7, or 14 days. Electroretinography (ERG), optical coherence tomography, blood flow and vascular oxygen tension imaging, and morphological and biochemical evaluations were performed in both eyes. Reduced ERG b-wave amplitudes and delayed implicit times were reported at 3, 7, and 14 days following BCCAO. Total retinal blood flow, MO2, and DO2 were reduced in all BCCAO groups. OEF was increased in both 3- and 7-day groups, while no significant difference was observed in OEF at 14 days compared to the sham group. At 14 days following BCCAO, total and inner retinal layer thickness was reduced, while the outer nuclear layer thickness and gliosis were increased. There was an increase in nuclei containing fragmented DNA at 3 days following BCCAO. The compensatory elevation in OEF following BCCAO did not meet the tissue demand, resulting in the subsequent reduction of MO2. The associations between retinal MO2, DO2, and retinal function were shown to be significant in the sequelae of persistent ischemia. In sum, measurements of DO2, MO2, and OEF may become useful for characterizing salvageable tissue in visionthreatening pathologies. Keywords Retinal ischemia . Chronic hypoperfusion . Oxygen metabolism . Oxygen delivery . Oxygen extraction fraction . Penumbra
Introduction Retinal ischemia has been implicated to play a significant role in vision-threatening diseases, including retinal vascular occlusions, ocular ischemic syndrome, retinopathy of prematurity, diabetic retinopathy, and glaucoma [1]. Specifically, the high metabolic demands of light-processing events in the retina are sustained by both oxygen and glucose delivered from two arterial systems: the choroid which predominately supplies the outer retina and the central retinal artery which * Mahnaz Shahidi [email protected] 1
Department of Ophthalmology, University of Southern California, Los Angeles, CA, USA
2
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA
predominately supplies the inner retina [2]. If the metabolic demands are not
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