Investigative Ophthalmology & Visual Science, Vol. 30, No. 4, April 1989 Copyright © Association for Research in Vision and Ophthalmology Effects of Hyperoxia on the Oxygen Distribution in the Intact Cat Retina Robert A. Linsenmeier*f and Charles M. Yanceyf Double-barreled oxygen microelectrodes were used to measure the distribution of oxygen within the dark adapted cat retina during systemic hyperoxia (100% O2 inspired). Oxygen tension (PO2) de- creased monotonically from the choroid to the vitreous humor in most cases, showing that a greater portion of the retina was supplied by the choroid during hyperoxia than during normoxia. In the proximal half of the retina the PO2 increased during hyperoxia by an average of about 40 mm Hg, while the increase in the distal retina was larger. At the choroid the average increase in PO2 was about ISO mm Hg. Analysis of the oxygen profiles showed that photoreceptor oxygen consumption was unchanged during hyperoxia. Retinal PO2 increased rapidly at the beginning of hyperoxia, and often partially recovered from its peak value during hyperoxia, even in the distal retina, suggesting that the choroidal circulation may have some limited autoregulatory capacity. As in normoxia, retinal illumina- tion led to an increase in PO2 in the distal retina, due to a decrease in oxygen consumption. The light-evoked increase in PO2 was larger during hyperoxia, but the underlying change in oxygen consumption was probably the same as in normoxia. Invest Ophthalmol Vis Sci 30:612-618,1989 Numerous studies have shown that adequate has been controversial. Some investigators suggest amounts of oxygen are essential for normal retinal that diffusion of oxygen from the choroid is essential function, and in higher mammals both the choroidal in causing vasoconstriction of retinal vessels in hy- and retinal circulations are necessary (eg, refs. 1-3). peroxia4 but the m'ost recent data15 suggest that oxy- When the retinal circulation is compromised, it is gen carried by the retinal circulation must be impor- believed that the choroidal circulation may be able to tant. Less is known' about the PO2 in the distal retina supply most or all of the retina, provided that the during hyperoxia, since this cannot be measured with 4 5 arterial oxygen tension (PaO2) is elevated, ' but hy- vitreal electrodes. Choroidal blood flow is generally peroxia can have deleterious effects as well. If in- considered to be passive with respect to changes in 6 1617 spired PO2 is very high, retinal oxidative metabolism PaO2, and since oxygen extraction from the cho- + + 7 218 and Na -K ATPase activity are reduced. The retina roid is small choroidal PO2 would be expected to is also more susceptible to light damage in hyperoxic rise substantially when PaO2 is elevated. This has, in monkeys than in normoxic ones.8 Finally, the best fact, been demonstrated in the pig retina.19 example of the detrimental effect of hyperoxia is that The current work was undertaken to provide data it prevents normal retinal vascular development in on the oxygen distribution across the retina during premature infants (eg, ref. 9). hyperoxia, since this basic information is important Measurements of vitreal PO2 have shown that in several of the contexts mentioned above. The ef- inner retinal PO2 is reasonably well regulated during fect of light on the oxygen distribution has been eval- hyperoxia,10 due to the constriction of retinal ves- uated, since this has even more dramatic effects dur- sels""13 and the consequent reduction of retinal ing hyperoxia than during normoxia.3 Modelling of blood flow.12"14 The mechanism of the constriction oxygen transport has been employed to address issues related to retinal oxygen consumption. From the *Departments of Biomedical Engineering and Neuro- biology and Physiology and the tlnterdepartmental Graduate Pro- Materials and Methods gram in Neuroscience, Northwestern University, Evanston, Illi- nois. The methods for animal preparation, recording Supported by NIH grant EY-05034, Bethesda, Maryland, and and visual stimulation were the same as those pre- the Whitaker Foundation. viously published.320 Fourteen adult cats were used Submitted for publication: February 18, 1988; accepted October in this study. We have adhered to the ARVO Resolu- 26, 1988. tion on the Use of Animals in Research. During nor- Reprint requests: Dr. Robert A. Linsenmeier, Biomedical Engi- neering Department, Northwestern University, 2145 Sheridan moxia the animals breathed air, supplemented when Road, Evanston, IL 60208. necessary with enough O2 to keep arterial PO2 above 612 Downloaded from iovs.arvojournals.org on 09/26/2021 613 No. 4 HYPEROXIC EFFECTS ON RETINAL PO2 / Linsenmeier and Yoncey 85 mm Hg. Hyperoxia was induced with 100% in- Normoxia spired O2. During normoxia.the average PaO2 was 98.6 ± 13.0 mm Hg (mean ± SD; n = 27) and during hyperoxia it was 415.5 ± 72.3 mm Hg (n = 54). Arte- rial pH and PCO2 were 7.42 ± 0.04 and 31.3 ± 5.6 mm Hg during normoxia, and were unchanged (by paired t-test) during hyperoxia. Arterial blood pres- sure was generally unchanged by hyperoxia. The du- ration of hyperoxia varied from 6 min to about 2 hr depending on the type of experiment being per- formed. Results Oxygen Profiles in the Dark-Adapted Retina The distribution of oxygen in the dark-adapted ret- ina was measured during electrode penetrations and 0 L withdrawals. During penetrations the electrode was 100 80 60 40 20 0 advanced in 3 /im steps from the vitreal surface to the choroid, and at approximately 20 uta intervals the Retinal depth (%) current was allowed to stabilize and was recorded. Fig. 1. Profiles of retinal oxygen tension during electrode with- Withdrawals were performed with the electrode drawal from choroid (100% depth) to vitreous (0% depth) during moving in 1 fim steps at 1 or 1.5 /xm per sec. The (A) normoxia, and (B) and (C) hyperoxia. Each profile is a single retinal depth of the electrode was assessed with the withdrawal during dark adaptation; 100% depth was the point at local electroretinogram, which was recorded with the which the reference barrel recorded the increase in potential across the retinal pigment epithelium, which coincided with the beginning reference barrel.3 Recordings were usually made in or of the PO2 decrease. Zero was taken to be the point at which the near the area centralis. Figure 1 shows oxygen profiles ERG b-wave changed from a negative intraretinal polarity to a (ie, PO2 as a function of retinal depth) measured dur- positive vitreal polarity. B was recorded in the area centralis (cat ing electrode withdrawals during air breathing (nor- 31). C was recorded during hyperoxia near the superior retinal moxia) (Fig. 1 A) and hyperoxia (Fig. IB) in the same artery and shows a peak in PO2 in the proximal retina (cat 31). animal. The typical normoxic profile320 showed a rel- atively high PO at the choroid and then a steep gra- 2 profile in most of the retina is more likely to be simi- dient, culminating in a PO of close to zero mm Hg 2 lar to that in Figure IB. between 65 and 85% retinal depth. The PO then rose 2 A substantial variation was observed in choroidal in the inner half of the retina, where the PO2 averaged PO2 during both normoxia and hyperoxia, as shown about 20 mm Hg. During hyperoxia the PO2 in- creased throughout the retina, but the most dramatic in Figure 2. During normoxia the average choroidal change was in the outer retina, where the minimum PO2 was 77.2 ± 20.7 mm Hg (n = 24), while during was eliminated. Since profiles were never measured hyperoxia it was 230 ± 87 mm Hg (n = 18). The in exactly the same location twice, this type of mea- corresponding arterial PO2s were 98.6 ± 11-0 and 436 surement was not suitable for determining the size of ±57 mm Hg. Thus, in both absolute and relative terms, the difference between arterial and choroidal changes in PO2 at any depth. They did show, how- ever, that in most cases (seven of eight penetrations PO2 was greater during hyperoxia. and 15 of 20 withdrawals in eight cats), PO2 increased monotonically, but not linearly, from the vitreal sur- Oxygen Consumption during Hyperoxia face to the choroid. The slope of the profile in the As described in the previous paper,20 oxygen pro- distal half of the retina was usually at least twice as files can be subjected to a steady-state diffusion analy- great as the slope in the proximal half of the retina. sis that allows estimation of the parameter Q/Dk, Several profiles showed the same features as de- which includes consumption per unit volume of tis- scribed above in the distal retina, but also had a rela- sue per time (Q), oxygen solubility (k) and oxygen tive maximum in PO2 in the proximal retina. The diffusion coefficient (D). As in the previous paper, the largest effect of this type was observed close to the avascular layer was divided into three sublayers superior retinal artery (Fig. 1C). Since this type of whose thicknesses were determined by fitting data to profile was observed only very near large vessels, the the model. The layer closest to the choroid (0 < x Downloaded from iovs.arvojournals.org on 09/26/2021 614 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / April 1989 Vol. 30 400 6 200 0 L ' 0 100 200 300 400 500 600 Arterial PO2 (mm Hg) Fig. 2. Choroidal PO2 as a function of arterial PO2 during nor- 30 mm Hg moxia (left group of points) and hyperoxia (right group of points). 100% oxygen The solid line connects the means of arterial and choroidal PO2 5 min under the two conditions.