Oxygen profiles and oxygen consumption in the isolated mouse retina

Linsenmeier, Robert A.; Dmitriev, Andrey V.; Dmitriev, Alexander A.

doi:10.1016/j.exer.2023.109554

Cited by 3 publications

(10 citation statements)

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“…We recorded PO 2 in isolated mouse retina with O 2 -sensitive microelectrodes in darkness and light at different retinal depths and fitted a diffusion model to the data to extract QO 2 . In preparation for this work, we found previously with recordings of [K + ] o in this preparation that 1 Hz flicker produced larger changes than 10 Hz flicker ( Dmitriev et al, 2022 ) and that four- and five-layer models of oxygen diffusion and consumption provided a good fit to profiles of PO 2 as a function of retinal depth ( Linsenmeier et al, 2023 ).…”

Section: Introductionmentioning

confidence: 79%

“…Animal experiments were performed in accordance with the Association for Research in Vision and Ophthalmology Statement for the Use of Animals in Ophthalmic and Vision Research and were approved by Northwestern University's Institutional Animal Care and Use Committee. The retinal preparation was as previously described ( Dmitriev et al, 2021 , 2022 ; Linsenmeier et al, 2023 ). Adult male C57BL/6J mice were dark-adapted for >3 h, anesthetized with 3% isoflurane in air, and killed by cervical dislocation.…”

Section: Methodsmentioning

confidence: 99%

“…This supply was enough to ensure that the entire tissue had nonzero PO 2 . Results are reported from 10 retinas from 10 animals; five were the same as in Linsenmeier et al (2023) and five were different.…”

Section: Methodsmentioning

confidence: 99%

“…Values at the end of 20 s of flicker were also plotted as a function of distance. A one-dimensional, steady-state, four–layer model of oxygen diffusion and consumption ( Linsenmeier et al, 2023 ) was fitted to the dark values. A one-dimensional model implies that there are no lateral O 2 gradients, which is a reasonable assumption for the isolated retina of an animal with little variation of cell density with eccentricity.…”

Section: Methodsmentioning

confidence: 99%

“…The solution to these equations, subject to matching of PO 2 and flux at the boundaries between layers is given in Appendix 2 of Linsenmeier et al (2023) . The model parameters were iteratively adjusted to determine the set of parameters that gave the best fit to the data.…”

Section: Methodsmentioning

confidence: 99%

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Increased Retinal Metabolism Induced by Flicker in the Isolated Mouse Retina

Linsenmeier,

Dmitriev

2024

eNeuro

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Both the retina and brain exhibit neurovascular coupling, increased blood flow during increased neural activity. In the retina increased blood flow can be evoked by flickering light, but the magnitude of the metabolic change that underlies this not known. Local changes in oxygen consumption (QO2) are difficult to measure in vivo when both supply and demand are changing. Here we isolated the C57BL/6J mouse retina and supplied it with oxygen from both sides of the tissue. Microelectrode recordings of PO2were made in darkness and during 20 sec of high scotopic flickering light at 1 Hz. Flicker led to a PO2increase in the outer retina and a decrease in the inner retina, indicating that outer retinal QO2(QOR) decreased and inner retinal QO2(QIR) increased. A four-layer oxygen diffusion model was fitted to PO2values obtained in darkness and at the end of flicker to determine the values of QORand QIR. QORin flicker was 76 ± 14% (mean and SD, n=10) of QORin darkness. The increase in QIRwas smaller, 6.4 ± 5.0%. These metabolic changes are likely smaller than the maximum changes, because with no regeneration of pigment in the isolated retina, we limited the illumination. Further modeling indicated that at high illumination, QIRcould increase by up to 45%, which is comparable to the magnitude of flow changes. This suggests that the blood flow increase is at least roughly matched to the increased metabolic demands of activity in the retina.Significance StatementNeural activity increases blood flow in the inner half of the retina as in the brain, but the underlying change in metabolism has been difficult to measure. Here we have measured the increase in metabolism (oxygen consumption, QO2) in mouse retina during flicker. Flicker at high scotopic illumination increased inner retinal QO2by less than 10% compared to darkness, considerably smaller in magnitude than the well-known light-evoked decrease in QO2in the outer retina under the same conditions. In the brain, the blood flow increase is larger than is required by the increase in QO2, but in the retina the increase in metabolism and blood flow appear to be more closely matched.

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Section: Introductionmentioning

confidence: 79%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Increased Retinal Metabolism Induced by Flicker in the Isolated Mouse Retina

Linsenmeier,

Dmitriev

2024

eNeuro

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pH in the vertebrate retina and its naturally occurring and pathological changes

Dmitriev,

Linsenmeier

2025

Progress in Retinal and Eye Research

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Characterization of the Retinal Circulation of the Mouse

Shang,,

Schallek

2024

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.Mice are highly used in retinal research because, like humans, mice have vascularized retinas and choroidal circulation. Although the retinal circulation has been well-characterized in development, its stability during adulthood is less understood. To examine this network, we quantified several key metrics of the trilaminar vasculature.METHODS. We used mice (n = 15) with transgenic fluorescent NG2-DsRed ( JX: #00824), a vascular-associated label in the retina. One eye per mouse was imaged using confocal microscopy (Nikon A1 Ti2 Eclipse) and traced with ImageJ SNT tools. Using an adaptive optics scanning light ophthalmoscope, additional mice (n = 3) were imaged at single-cell resolution within the living eye to measure the same vasculature. RESULTS.Across mice, we found a stable retinal circulation that formed and maintained a trilaminar stratification throughout early adulthood at all eccentricities. Bridging these layers, microvessels had five distinct anatomical branching patterns. The superficial, intermediate, and deep plexuses increased in density with depth: 16.14 ± 3.61 mm/mm 2 , 22.14 ± 6.86 mm/mm 2 , and 31.01 ± 6.24 mm/mm 2 , respectively. This patterning was not impacted by eccentricity or age (13-61 weeks). Similar metrics were achieved using adaptive optics scanning light ophthalmoscope in vivo with the same analysis pipeline.CONCLUSIONS. The mouse retinal vasculature was stable up to 50 weeks of age, providing a robust and extensive baseline dataset with which models of retinal vascular and neural disease may be compared. Vessels connecting the laminae were more complex than previously reported and represented a uniquely vulnerable population due to their relatively low density.

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Oxygen profiles and oxygen consumption in the isolated mouse retina

Cited by 3 publications

References 34 publications

Increased Retinal Metabolism Induced by Flicker in the Isolated Mouse Retina

Increased Retinal Metabolism Induced by Flicker in the Isolated Mouse Retina

pH in the vertebrate retina and its naturally occurring and pathological changes

Characterization of the Retinal Circulation of the Mouse

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