Retinal oxygen extraction in humans

René M Werkmeister, Doreen Schmidl, Gerold Aschinger, Veronika Doblhoff-Dier, Stefan Palkovits, Magdalena Wirth, Gerhard Garhöfer, Robert A Linsenmeier, Rainer A Leitgeb, Leopold Schmetterer, René M Werkmeister, Doreen Schmidl, Gerold Aschinger, Veronika Doblhoff-Dier, Stefan Palkovits, Magdalena Wirth, Gerhard Garhöfer, Robert A Linsenmeier, Rainer A Leitgeb, Leopold Schmetterer

Abstract

Adequate function of the retina is dependent on proper oxygen supply. In humans, the inner retina is oxygenated via the retinal circulation. We present a method to calculate total retinal oxygen extraction based on measurement of total retinal blood flow using dual-beam bidirectional Doppler optical coherence tomography and measurement of oxygen saturation by spectrophotometry. These measurements were done on 8 healthy subjects while breathing ambient room air and 100% oxygen. Total retinal blood flow was 44.3 ± 9.0 μl/min during baseline and decreased to 18.7 ± 4.2 μl/min during 100% oxygen breathing (P < 0.001) resulting in a pronounced decrease in retinal oxygen extraction from 2.33 ± 0.51 μl(O2)/min to 0.88 ± 0.14 μl(O2)/min during breathing of 100% oxygen. The method presented in this paper may have significant potential to study oxygen metabolism in hypoxic retinal diseases such as diabetic retinopathy.

Figures

Figure 1. Sample measurement in a healthy…
Figure 1. Sample measurement in a healthy subject.
(a) Fundus image and OCT scanning patterns used to measure all retinal vessels entering the optic nerve head to measure total retinal blood flow. Black bars indicate the measurement locations. (b,c) Magnification of the fundus image during breathing room air and 100% oxygen, respectively. Vasoconstriction of retinal artery and vein can clearly be seen. (d,e) Time course of retinal arterial and venous blood velocity during breathing room air and breathing 100% oxygen respectively over approximately 4 cardiac cycles.
Figure 2. % change in total retinal…
Figure 2. % change in total retinal blood flow (Q), arterial oxygen content (cO2,CRA), venous oxygen content (cO2,CRV), arteriovenous difference in oxygen content (cO2,DIFF) and retinal oxygen extraction (extO2) in response to 100% oxygen breathing (n = 8).
Data are presented as means ± SD.

References

    1. Pascolini D. & Mariotti S. P. Global estimates of visual impairment: 2010. Br J Ophthalmol 96, 614–618, 10.1136/bjophthalmol-2011-300539 (2012).
    1. Pemp B. & Schmetterer L. Ocular blood flow in diabetes and age-related macular degeneration. Can J Ophthalmol 43, 295–301, 10.3129/i08-049 (2008).
    1. Cherecheanu A. P., Garhofer G., Schmidl D., Werkmeister R. & Schmetterer L. Ocular perfusion pressure and ocular blood flow in glaucoma. Curr Opin Pharmacol 13, 36–42, 10.1016/j.coph.2012.09.003 (2013).
    1. Pournaras C. J., Rungger-Brandle E., Riva C. E., Hardarson S. H. & Stefansson E. Regulation of retinal blood flow in health and disease. Prog Retin Eye Res 27, 284–330, 10.1016/j.preteyeres.2008.02.002 (2008).
    1. Wangsa-Wirawan N. D. & Linsenmeier R. A. Retinal oxygen: fundamental and clinical aspects. Arch Ophthalmol 121, 547–557, 10.1001/archopht.121.4.547 (2003).
    1. Cringle S. J. & Yu D. Y. Oxygen supply and consumption in the retina: implications for studies of retinopathy of prematurity. Doc Ophthalmol 120, 99–109, 10.1007/s10633-009-9197-2 (2010).
    1. Whalen W. J., Riley J. & Nair P. A microelectrode for measuring intracellular PO2. J Appl Physiol 23, 798–801 (1967).
    1. Tsacopoulos M. & Lehmenkuhler A. A double-barrelled Pt-microelectrode for simultaneous measurement of PO2 and bioelectrical activity in excitable tissues. Experientia 33, 1337–1338 (1977).
    1. Linsenmeier R. A. & Yancey C. M. Improved fabrication of double-barreled recessed cathode O2 microelectrodes. Journal of applied physiology 63, 2554–2557 (1987).
    1. Pournaras C. J., Riva C. E., Tsacopoulos M. & Strommer K. Diffusion of O2 in the retina of anesthetized miniature pigs in normoxia and hyperoxia. Exp Eye Res 49, 347–360 (1989).
    1. Alder V. A., Cringle S. J. & Constable I. J. The retinal oxygen profile in cats. Invest Ophthalmol Vis Sci 24, 30–36 (1983).
    1. Cringle S. J., Yu D. Y. & Alder V. A. Intraretinal oxygen tension in the rat eye. Graefes Arch Clin Exp Ophthalmol 229, 574–577 (1991).
    1. Ahmed J., Braun R. D., Dunn R. Jr. & Linsenmeier R. A. Oxygen distribution in the macaque retina. Invest Ophthalmol Vis Sci 34, 516–521 (1993).
    1. Birol G., Wang S., Budzynski E., Wangsa-Wirawan N. D. & Linsenmeier R. A. Oxygen distribution and consumption in the macaque retina. Am J Physiol Heart Circ Physiol 293, H1696–1704, 10.1152/ajpheart.00221.2007 (2007).
    1. Doblhoff-Dier V. et al.. Measurement of the total retinal blood flow using dual beam Fourier-domain Doppler optical coherence tomography with orthogonal detection planes. Biomed Opt Express 5, 630–642, 10.1364/BOE.5.000630 (2014).
    1. Hammer M., Vilser W., Riemer T. & Schweitzer D. Retinal vessel oximetry-calibration, compensation for vessel diameter and fundus pigmentation, and reproducibility. J Biomed Opt 13, 054015, 10.1117/1.2976032 (2008).
    1. Geirsdottir A. et al.. Retinal vessel oxygen saturation in healthy individuals. Invest Ophthalmol Vis Sci 53, 5433–5442, 10.1167/iovs.12-9912 (2012).
    1. Chung C. K. & Linsenmeier R. A. Effect of carbogen (95% O2/5% CO2) on retinal oxygenation in dark-adapted anesthetized cats. Curr Eye Res 32, 699–707, 10.1080/02713680701459250 (2007).
    1. Linsenmeier R. A. & Yancey C. M. Effects of hyperoxia on the oxygen distribution in the intact cat retina. Invest Ophthalmol Vis Sci 30, 612–618 (1989).
    1. Palkovits S. et al.. Retinal oxygen metabolism during normoxia and hyperoxia in healthy subjects. Invest Ophthalmol Vis Sci 55, 4707–4713, 10.1167/iovs.14-14593 (2014).
    1. Werkmeister R. M. et al.. Bidirectional Doppler Fourier-domain optical coherence tomography for measurement of absolute flow velocities in human retinal vessels. Opt Lett 33, 2967–2969 (2008).
    1. Werkmeister R. M. et al.. Response of retinal blood flow to systemic hyperoxia as measured with dual-beam bidirectional Doppler Fourier-domain optical coherence tomography. PLoS One 7, e45876, 10.1371/journal.pone.0045876 (2012).
    1. Werkmeister R. M. et al.. Measurement of absolute blood flow velocity and blood flow in the human retina by dual-beam bidirectional Doppler fourier-domain optical coherence tomography. Invest Ophthalmol Vis Sci 53, 6062–6071, 10.1167/iovs.12-9514 (2012).
    1. Hammer M. et al.. Diabetic patients with retinopathy show increased retinal venous oxygen saturation. Graefes Arch Clin Exp Ophthalmol 247, 1025–1030, 10.1007/s00417-009-1078-6 (2009).
    1. Buerk D. G., Shonat R. D., Riva C. E. & Cranstoun S. D. O2 gradients and countercurrent exchange in the cat vitreous humor near retinal arterioles and venules. Microvasc Res 45, 134–148, 10.1006/mvre.1993.1013 (1993).
    1. Nielsen H. B., Madsen P., Svendsen L. B., Roach R. C. & Secher N. H. The influence of PaO2, pH and SaO2 on maximal oxygen uptake. Acta physiologica Scandinavica 164, 89–87, 10.1046/j.1365-201X.1998.00405.x (1998).
    1. Mason R. J. et al.. Murray and Nadel’s Textbook of Respiratory Medicine. 2 edn, (Saunders W.B., 1994).
    1. Leow M. K. Configuration of the hemoglobin oxygen dissociation curve demystified: a basic mathematical proof for medical and biological sciences undergraduates. Advances in physiology education 31, 198–201, 10.1152/advan.00012.2007 (2007).
    1. Feke G. T. et al.. Blood flow in the normal human retina. Invest Ophthalmol Vis Sci 30, 58–65 (1989).
    1. Straatsma B. R., Foos R. Y. & Spencer L. M. in In New Orleans Academy of Ophthalmology Symposium on Retina and Retinal Surgery (St. Louis: CV Mosby, 1969).
    1. Aleman T. S. et al.. Inner retinal abnormalities in X-linked retinitis pigmentosa with RPGR mutations. Invest Ophthalmol Vis Sci 48, 4759–4765, 10.1167/iovs.07-0453 (2007).
    1. Hickam J. B. & Frayser R. Studies of Retinal Circulation in Man - Observations on Vessel Diameter Arteriovenous Oxygen Difference and Mean Circulation Time. Circulation 33, 302–& (1966).
    1. Riva C. E., Grunwald J. E., Sinclair S. H. & Petrig B. L. Blood velocity and volumetric flow rate in human retinal vessels. Invest Ophthalmol Vis Sci 26, 1124–1132 (1985).
    1. Grunwald J. E., Riva C. E., Baine J. & Brucker A. J. Total retinal volumetric blood flow rate in diabetic patients with poor glycemic control. Invest Ophthalmol Vis Sci 33, 356–363 (1992).
    1. Polska E., Kircher K., Ehrlich P., Vecsei P. V. & Schmetterer L. RI in central retinal artery as assessed by CDI does not correspond to retinal vascular resistance. Am J Physiol Heart Circ Physiol 280, H1442–1447 (2001).
    1. Wang Y., Bower B. A., Izatt J. A., Tan O. & Huang D. Retinal blood flow measurement by circumpapillary Fourier domain Doppler optical coherence tomography. J Biomed Opt 13, 064003, 10.1117/1.2998480 (2008).
    1. Baumann B. et al.. Total retinal blood flow measurement with ultrahigh speed swept source/Fourier domain OCT. Biomed Opt Express 2, 1539–1552, 10.1364/BOE.2.001539 (2011).
    1. Garhofer G., Werkmeister R., Dragostinoff N. & Schmetterer L. Retinal blood flow in healthy young subjects. Invest Ophthalmol Vis Sci 53, 698–703, 10.1167/iovs.11-8624 (2012).
    1. Sehi M. et al.. Retinal blood flow in glaucomatous eyes with single-hemifield damage. Ophthalmology 121, 750–758, 10.1016/j.ophtha.2013.10.022 (2014).
    1. Wang L., Tornquist P. & Bill A. Glucose metabolism in pig outer retina in light and darkness. Acta physiologica Scandinavica 160, 75–81, 10.1046/j.1365-201X.1997.00030.x (1997).
    1. Medrano C. J. & Fox D. A. Oxygen consumption in the rat outer and inner retina: light- and pharmacologically-induced inhibition. Exp Eye Res 61, 273–284 (1995).
    1. Braun R. D., Linsenmeier R. A. & Goldstick T. K. Oxygen consumption in the inner and outer retina of the cat. Invest Ophthalmol Vis Sci 36, 542–554 (1995).
    1. Kur J., Newman E. A. & Chan-Ling T. Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease. Prog Retin Eye Res 31, 377–406, 10.1016/j.preteyeres.2012.04.004 (2012).
    1. Wanek J., Teng P. Y., Blair N. P. & Shahidi M. Inner retinal oxygen delivery and metabolism under normoxia and hypoxia in rat. Invest Ophthalmol Vis Sci 54, 5012–5019, 10.1167/iovs.13-11887 (2013).
    1. Song W. et al.. A combined method to quantify the retinal metabolic rate of oxygen using photoacoustic ophthalmoscopy and optical coherence tomography. Scientific Reports 4, 6525, 10.1038/srep06525 (2014).
    1. Blaszczyk W. M., Straub H. & Distler C. GABA content in the retina of pigmented and albino rats. Neuroreport 15, 1141–1144 (2004).
    1. Riva C. E., Pournaras C. J. & Tsacopoulos M. Regulation of local oxygen tension and blood flow in the inner retina during hyperoxia. Journal of applied physiology 61, 592–598 (1986).
    1. Yu D. Y., Cringle S. J. & Alder V. A. The response of rat vitreal oxygen tension to stepwise increases in inspired percentage oxygen. Invest Ophthalmol Vis Sci 31, 2493–2499 (1990).
    1. Schmetterer L. et al.. The effect of hyperoxia and hypercapnia on fundus pulsations in the macular and optic disc region in healthy young men. Exp Eye Res 61, 685–690 (1995).
    1. Garhofer G. et al.. Use of the retinal vessel analyzer in ocular blood flow research. Acta Ophthalmol 88, 717–722, 10.1111/j.1755-3768.2009.01587.x (2010).
    1. Liu W., Jiao S. & Zhang H. F. Accuracy of retinal oximetry: a Monte Carlo investigation. J Biomed Opt 18, 066003, 10.1117/1.JBO.18.6.066003 (2013).
    1. Hardarson S. H. & Stefansson E. Oxygen saturation in branch retinal vein occlusion. Acta Ophthalmol 90, 466–470, 10.1111/j.1755-3768.2011.02109.x (2012).
    1. Hardarson S. H. et al.. Automatic retinal oximetry. Invest Ophthalmol Vis Sci 47, 5011–5016, 10.1167/iovs.06-0039 (2006).
    1. Traustason S. et al.. Retinal oxygen saturation in patients with systemic hypoxemia. Invest Ophthalmol Vis Sci 52, 5064–5067, 10.1167/iovs.11-7275 (2011).
    1. Palkovits S. et al.. Measurement of retinal oxygen saturation in patients with chronic obstructive pulmonary disease. Invest Ophthalmol Vis Sci 54, 1008–1013, 10.1167/iovs.12-10504 (2013).
    1. Palkovits S. et al.. Regulation of retinal oxygen metabolism in humans during graded hypoxia. Am J Physiol Heart Circ Physiol 307, H1412–1418, 10.1152/ajpheart.00479.2014 (2014).

Source: PubMed

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