Retinal oxygen: from animals to humans

Abstract

This article discusses retinal oxygenation and retinal metabolism by focusing on measurements made with two of the principal methods used to study O2 in the retina: measurements of PO2 with oxygen-sensitive microelectrodes in vivo in animals with a retinal circulation similar to that of humans, and oximetry, which can be used non-invasively in both animals and humans to measure O2 concentration in retinal vessels. Microelectrodes uniquely have high spatial resolution, allowing the mapping of PO2 in detail, and when combined with mathematical models of diffusion and consumption, they provide information about retinal metabolism. Mathematical models, grounded in experiments, can also be used to simulate situations that are not amenable to experimental study. New methods of oximetry, particularly photoacoustic ophthalmoscopy and visible light optical coherence tomography, provide depth-resolved methods that can separate signals from blood vessels and surrounding tissues, and can be combined with blood flow measures to determine metabolic rate. We discuss the effects on retinal oxygenation of illumination, hypoxia and hyperoxia, and describe retinal oxygenation in diabetes, retinal detachment, arterial occlusion, and macular degeneration. We explain how the metabolic measurements obtained from microelectrodes and imaging are different, and how they need to be brought together in the future. Finally, we argue for revisiting the clinical use of hyperoxia in ophthalmology, particularly in retinal arterial occlusions and retinal detachment, based on animal research and diffusion theory.

OCT Angiography Changes in the 3 Parafoveal Retinal Plexuses in Response to Hyperoxia

“…The choroidal circulation is thought to provide relatively constant flow, 33–36 whereas the retinal circulation varies in response to changes in partial pressure of oxygen (pO 2 ). 37 In recent animal hypoxia experiments by Yi et al, retinal blood flow increased so much that total oxygen extraction actually increased.…”

The 3D Retinal Capillary Circulation in Pigs Reveals a Predominant Serial Organization

“…The oxygen partial pressure varies significantly across neuronal layers. 1,23 The distance between capillaries and the consumption of oxygen determines the relative oxygen content in the immediate environment of each capillary, which may be conceptualized as a cylinder around capillaries (Krogh's cylinder 24 ) although this concept suggests a normoxic/anoxic frontier instead of a continuum. Nevertheless, within a specific layer (i.e., within a given neuronal population) it can be assumed that the distribution of microvessels is paralleled by the local oxygen content and, hence, that the intercapillary distance is a function of the size of Krogh's cylinder.…”

“…This rather long pathway may participate in the high coefficient of extraction of oxygen in retinal vessels. 1 The neural consequences of local hypoxia in the retina may be deduced from the Krogh's cylinders concept; that is, the more distant a neuron is from its source of oxygen, the more likely it is to be affected by decreased plasma oxygen saturation. Hence, in case of decreased blood flow without obstruction, hypoxia (and, hence, ischemia) will affect mostly the outer plexiform and inner nuclear layers around collecting venules (i.e., the area most distant from arterioles).…”

“…Most neurons have little tolerance to ischemia; yet paradoxically, the blood flow of the retina relative to tissue weight is low compared to other tissues. 1 This stresses the importance of an optimally designed angioarchitecture as well as a stringent adaptation of blood flow to local oxygen demand. This is illustrated in the fovea, where the width of the foveal pit closely matches the size of the foveal avascular zone.…”

Spectroscopic Doppler analysis for visible-light optical coherence tomography

“…[1][2][3] Previous studies suggested that retinal metabolic abnormalities play an important role in the development of DR 2, 4,5 and that rMRO 2 is a potential biomarker for early diagnosis of DR before irreversible damage occurs. [6][7][8] In order to calculate rMRO 2 , we need to measure oxygen saturation (sO 2 ) and the flow rate in major retinal blood vessels, both of which can be effectively quantified simultaneously by visible-light optical coherence tomography (vis-OCT).…”