Increased Retinal Metabolism Induced by Flicker in the Isolated Mouse Retina

Abstract

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.