Oxygen consumption in the rat outer and inner retina: Light- and pharmacologically-induced inhibition

Medrano, Carlos J.; Fox, Donald A.

doi:10.1016/s0014-4835(05)80122-8

Cited by 102 publications

(111 citation statements)

References 60 publications

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“…14, 64 Okawa et al 1 calculated that a single mouse rod consumes 1 × 10 8 ATP per second in darkness and 2 × 10 7 ATP per second in light, which equates to a four-fold increase in energy consumption in darkness versus in light. The absolute number of ATP molecules consumed varies among species, age, lifestyle, and time of the day.…”

Section: Energy Consumption In Photoreceptorsmentioning

confidence: 99%

Glucose metabolism in mammalian photoreceptor inner and outer segments

Narayan

Chidlow

Wood

et al. 2017

Clinical Exper Ophthalmology

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Photoreceptors are the first-order neurons of the visual pathway, converting light into electrical signals. Rods and cones are the two main types of photoreceptors in the mammalian retina. Rods are specialized for sensitivity at the expense of resolution and are responsible for vision in dimly lit conditions. Cones are responsible for high acuity central vision and colour vision. Many human retinal diseases are characterized by a progressive loss of photoreceptors. Photoreceptors consist of four primary regions: outer segments, inner segments, cell bodies and synaptic terminals. Photoreceptors consume large amounts of energy, and therefore, energy metabolism may be a critical juncture that links photoreceptor function and survival. Cones require more energy than rods, and cone degeneration is the main cause of clinically significant vision loss in retinal diseases. Photoreceptor segments are capable of utilizing various energy substrates, including glucose, to meet their large energy demands. The pathways by which photoreceptor segments meet their energy demands remain incompletely understood. Improvements in the understanding of glucose metabolism in photoreceptor segments may provide insight into the reasons why photoreceptors degenerate due to energy failure. This may, in turn, assist in developing bio-energetic therapies aimed at protecting photoreceptors.

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Section: Energy Consumption In Photoreceptorsmentioning

confidence: 99%

Glucose metabolism in mammalian photoreceptor inner and outer segments

Narayan

Chidlow

Wood

et al. 2017

Clinical Exper Ophthalmology

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“…QO PR was recorded from isolated pairs of PN25 and PN90 mouse retinas. QO PR was determined polarographically and recorded continuously in the dark or during presentation of a rod-saturating light adapting stimulus as described (25,28).…”

Section: Rod Photoreceptor Oxygen Consumption (Qopr)mentioning

confidence: 99%

Bcl-x _L overexpression blocks bax-mediated mitochondrial contact site formation and apoptosis in rod photoreceptors of lead-exposed mice

Perkins

Poblenz

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Photoreceptor apoptosis and resultant visual deficits occur in humans and animals with inherited and disease-, injury-, and chemical-induced retinal degeneration. A clinically relevant mouse model of progressive rod photoreceptor-selective apoptosis was produced by low-level developmental lead exposure and studied in combination with transgenic mice overexpressing Bcl-xL only in the photoreceptors. A multiparametric analysis of rod apoptosis and mitochondrial structure-function was performed. Mitochondrial cristae topography and connectivity, matrix volume, and contact sites were examined by using 3D electron tomography. Leadinduced rod-selective apoptosis was accompanied by rod Ca 2؉ overload, rhodopsin loss, translocation of Bax from the cytosol to the mitochondria, decreased rod mitochondrial respiration and membrane potential, mitochondrial cytochrome c release, caspase-3 activation, and an increase in the number of mitochondrial contact sites. These effects occurred without mitochondrial matrix swelling, outer membrane rupture, caspase-8 activation, or Bid cleavage. Bcl-xL overexpression completely blocked all apoptotic events, except Ca 2؉ overload, and maintained normal rod mitochondrial function throughout adulthood. This study presents images of mitochondrial contact sites in an in vivo apoptosis model and shows that Bcl-xL overexpression blocks increased contact sites and apoptosis. These findings extend our in vitro retinal studies with Pb 2؉ and Ca 2؉ and suggest that developmental lead exposure produced rod-selective apoptosis without mitochondrial swelling by translocating cytosolic Bax to the mitochondria, which likely sensitized the Pb 2؉ and Ca 2؉ overloaded rod mitochondria to release cytochrome c. These results have relevance for therapies in a wide variety of progressive retinal and neuronal degenerations where Ca 2؉ overload, lead exposure, and͞or mitochondrial dysfunction occur.

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“…Furthermore, these effects are mediated by D2/D4-like, and not D1, dopamine receptors. An abstract describing these findings has been published (25 QOPR experiments used retinas from dark-adapted rats and were conducted under infrared illumination (26). The Na,KATPase enzyme studies were conducted under normal room light and began 1 hr after the onset of the light cycle.…”

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confidence: 99%

“…Each whole neural retina was placed into a 1.5-ml waterjacketed (37.0 ± 0.1°C) Gilson-type oxygen chamber containing Ringer's buffer with L-2-amino-4-phosphonobutyric acid (APB; 100 ,uM) plus kynurenic acid (Kyn; 5 mM) added. APB/Kyn were used to pharmacologically isolate photoreceptors from the remaining inner retina so that QOPR could be determined (26,27). QOPR of each retina was determined polarographically and was recorded continuously in the dark and during the presentation of a half-saturating or rodsaturating light adapting stimulus (26 37.0°C, and delivered in [1][2][3][4][5][6][7][8][9][10] ,ld through an inlet port on the Gilson chamber.…”

mentioning

confidence: 99%

“…For light-adaptation experiments, a dark-adapted retina was stimulated for 120 sec with either half rod-saturating or rod-saturating white light (32): the latter maximally reduced the dark-adapted QOPR (26). The developed to localize and assess the effects of dopamine on ROS-RIS Na,K-ATPase activity since ROS-RIS isolated using enzymatic dissociation had decreased plasma membrane integrity and Na,K-ATPase activity.…”

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confidence: 99%

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Dopamine inhibits mammalian photoreceptor Na+,K+-ATPase activity via a selective effect on the alpha3 isozyme.

Shulman

Fox

1996

Proc. Natl. Acad. Sci. U.S.A.

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The rat retina contains dopaminergic interplexiform cells that send processes to the outer plexiform layer where dopamine is released in a light-dependent manner. We report herein that physiologically relevant concentrations of dopamine inhibited ouabain-sensitive photoreceptor oxygen consumption in dark-and light-adapted rat retinas and inhibited Na+,K+-ATPase specific activity (EC 3.6.1.37) in a rat rod outer-inner segment preparation. Experiments with the selective Dt agonist fenoldopam or D2 agonist quinpirole and experiments with dopamine plus either the Di antagonist SCH23390 or D2/D4 antagonist clozapine showed that the inhibition of oxygen consumption and enzyme activity were mediated by D2/D4-like receptors. The amphetamineinduced release of dopamine, monitored by the inhibition of oxygen consumption, was blocked by L-2-amino-4-phosphonobutyric acid and kynurenic acid. Pharmacological and biochemical experiments determined that the IC50 values of ouabain for the cvl-low and a3-high ouabain affinity isozymes of photoreceptor Na+,K+-ATPase were -10-5 and _10-7 M, respectively, and that the D2/D4-like mediated inhibition of Na+,K+-ATPase was exclusively selective for the a3 isozyme. The dopamine-mediated inhibition of a3 first occurred at 5 nM, was maximal at 100 ,uM (-47%), had an IC50 value of 382 + 23 nM, and exhibited negative cooperativity (Hill coefficient, 0.27). Prior homogenization of the rod outer-inner segment completely prevented the long-lasting inhibition, suggesting that the effect was coupled to a second messenger. Although the physiological significance of our findings to photoreceptor function is unknown, we hypothesize that these results may have relevance for the temporal tuning properties of rods.

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Oxygen consumption in the rat outer and inner retina: Light- and pharmacologically-induced inhibition

Cited by 102 publications

References 60 publications

Glucose metabolism in mammalian photoreceptor inner and outer segments

Glucose metabolism in mammalian photoreceptor inner and outer segments

Bcl-x _L overexpression blocks bax-mediated mitochondrial contact site formation and apoptosis in rod photoreceptors of lead-exposed mice

Dopamine inhibits mammalian photoreceptor Na+,K+-ATPase activity via a selective effect on the alpha3 isozyme.

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Oxygen consumption in the rat outer and inner retina: Light- and pharmacologically-induced inhibition

Cited by 102 publications

References 60 publications

Glucose metabolism in mammalian photoreceptor inner and outer segments

Glucose metabolism in mammalian photoreceptor inner and outer segments

Bcl-x L overexpression blocks bax-mediated mitochondrial contact site formation and apoptosis in rod photoreceptors of lead-exposed mice

Dopamine inhibits mammalian photoreceptor Na+,K+-ATPase activity via a selective effect on the alpha3 isozyme.

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Bcl-x _L overexpression blocks bax-mediated mitochondrial contact site formation and apoptosis in rod photoreceptors of lead-exposed mice