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Biochemical adaptations of the retina and retinal pigment epithelium support a metabolic ecosystem in the vertebrate eye.

Mark A Kanow | Michelle M Giarmarco | Connor Sr Jankowski | Kristine Tsantilas | Abbi L Engel | Jianhai Du | Jonathan D Linton | Christopher C Farnsworth | Stephanie R Sloat | Austin Rountree | Ian R Sweet | Ken J Lindsay | Edward D Parker | Susan E Brockerhoff | Martin Sadilek | Jennifer R Chao | James B Hurley
eLife | 2017

Here we report multiple lines of evidence for a comprehensive model of energy metabolism in the vertebrate eye. Metabolic flux, locations of key enzymes, and our finding that glucose enters mouse and zebrafish retinas mostly through photoreceptors support a conceptually new model for retinal metabolism. In this model, glucose from the choroidal blood passes through the retinal pigment epithelium to the retina where photoreceptors convert it to lactate. Photoreceptors then export the lactate as fuel for the retinal pigment epithelium and for neighboring Müller glial cells. We used human retinal epithelial cells to show that lactate can suppress consumption of glucose by the retinal pigment epithelium. Suppression of glucose consumption in the retinal pigment epithelium can increase the amount of glucose that reaches the retina. This framework for understanding metabolic relationships in the vertebrate retina provides new insights into the underlying causes of retinal disease and age-related vision loss.

Pubmed ID: 28901286

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This is a list of tools and resources that we have found mentioned in this publication.


Thermo Fisher Scientific (tool)

RRID:SCR_008452

Commercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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IRDye 800CW Goat anti-Rabbit IgG (antibody)

RRID:AB_621843

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Glucose Transporter GLUT4 antibody (antibody)

RRID:AB_305554

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Glucose Transporter GLUT1 antibody [EPR3915] (antibody)

RRID:AB_10903230

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Glucose Transporter GLUT3 antibody (antibody)

RRID:AB_732609

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R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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B6.Cg-Tg(Nrl-EGFP)1Asw/J (organism)

RRID:IMSR_JAX:021232

Mus musculus with name B6.Cg-Tg(Nrl-EGFP)1Asw/J from IMSR.

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Glucose Transporter GLUT1 antibody [EPR3915] (antibody)

RRID:AB_10903230

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Odyssey CLx (software resource)

RRID:SCR_014579

A data analysis software developed to simplify and record data from fluorescent related assays such as Western Blots, EMSAs, and Western Assays. This software will consolidate all of the resulting data into one easy-to-track image, and thus removes the need for multiple exposures, as well as standardizing the resulting fluorescent bands without image saturation, blowout, or removed sensitivity. Odyssey CLx is capable of scanning multiple mini-blots, microplates, or slides at the same time.

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Leica Application Suite X (resource)

RRID:SCR_013673

Software for image capture, processing and analysis with Leica fluorescence and confocal microscopes.

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Fiji (software resource)

RRID:SCR_002285

Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.

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TrakEM2 (data processing software)

RRID:SCR_008954

An ImageJ plugin for morphological data mining, three-dimensional modeling and image stitching, registration, editing and annotation. Two independent modalities exist: either XML-based projects, working directly with the file system, or database-based projects, working on top of a local or remote PostgreSQL database. What can you do with it? * Semantic segmentation editor: order segmentations in tree hierarchies, whose template is exportable for reuse in other, comparable projects. * Model, visualize and export 3D. * Work from your laptop on your huge, remote image storage. * Work with an endless number of images, limited only by the hard drive capacity. Dozens of formats supported thanks to LOCI Bioformats and ImageJ. * Import stacks and even entire grids (montages) of images, automatically stitch them together and homogenize their histograms for best montaging quality. * Add layers conveniently. A layer represents, for example, one 50 nm section (for TEM) or a confocal section. Each layer has its own Z coordinate and thickness, and contains images, labels, areas, nodes of 3d skeletons, profiles... * Insert layer sets into layers: so your electron microscopy serial sections can live inside your optical microscopy sections. * Run any ImageJ plugin on any image. * Measure everything: areas, volumes, pixel intensities, etc. using both built-in data structures and segmentation types, and standard ImageJ ROIs. And with double dissectors! * Visualize RGB color channels changing the opacity of each on the fly, non-destructively. * Annotate images non-destructively with floating text labels, which you can rotate/scale on the fly and display in any color. * Montage/register/stitch/blend images manually with transparencies, semiautomatically, or fully automatically within and across sections, with translation, rigid, similarity and affine models with automatically extracted SIFT features. * Correct the lens distortion present in the images, like those generated in transmission electron microscopy. * Add alpha masks to images using ROIs, for example to split images in two or more parts, or to remove the borders of an image or collection of images. * Model neuronal arbors with 3D skeletons (with areas or radiuses), and synapses with connectors. * Undo all steps. And much more...

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