June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Connectomic reconstruction links human foveal cones to distinct circuitry in the center of the foveal pit
Author Affiliations & Notes
  • Dennis M Dacey
    Biological Structure, University of Washington, Seattle, Washington, United States
  • Orin Packer
    Biological Structure, University of Washington, Seattle, Washington, United States
  • Richard Schalek
    Molecular and Cell Biology, Harvard, Cambridge, Massachusetts, United States
  • Christine Curcio
    Ophthalmology, University of Alabama, Birmingham, Birmingham, Alabama, United States
  • Rachel O Wong
    Biological Structure, University of Washington, Seattle, Washington, United States
  • John E Dowling
    Molecular and Cell Biology, Harvard, Cambridge, Massachusetts, United States
  • Jeff Lichtman
    Molecular and Cell Biology, Harvard, Cambridge, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Dennis Dacey, None; Orin Packer, None; Richard Schalek, None; Christine Curcio, None; Rachel Wong, None; John Dowling, None; Jeff Lichtman, None
  • Footnotes
    Support  NIH R01 EY06678, NIH R01 EY015520, EyeSight Foundation of Alabama, Research to Prevent Blindness, Macula Foundation, Lowy Medical Resarch Institute
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1036. doi:
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      Dennis M Dacey, Orin Packer, Richard Schalek, Christine Curcio, Rachel O Wong, John E Dowling, Jeff Lichtman; Connectomic reconstruction links human foveal cones to distinct circuitry in the center of the foveal pit. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1036.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : In the macula, cone photoreceptors give rise to long axon-like processes (Henle fibers) that can project up to several hundred µm to circuitry displaced laterally from the foveal depression. However the precise localization of the synaptic terminals (pedicles) of the cones that occupy the very center of the fovea where visual acuity peaks has not been directly determined. Thus, the retinal location of the circuitry that arises from this critical cone population is unclear. Our purpose was to use volume electron microscopy to reconstruct the central-most foveal cones and directly connect the mosaic of inner segments to their pedicles via Henle fibers.

Methods : Eyes were acquired from a single 21 yr old male organ donor at the time of death. After corneal removal the open eyecup was immersed in oxygenated Ames medium and then fixed in 4% glutaraldehyde. The macular region was dissected, epoxy-embedded and serially sectioned at 65 nm from the photoreceptor layer to the inner limiting membrane using the Automated Tape Ultramicrotome (ATUM) method. A 250 x 250 µm region centered on the fovea was imaged at 6 nm resolution and 1500 serial sections were used for volume reconstruction (TrakEM2).

Results : A circular patch of 186 neighboring cones at the precise foveal center was reconstructed. The Henle fibers of the central most cones extended vertically with little lateral displacement and gave rise to a point-to-point topographic array of large morphologically distinct pedicles localized to the center of the foveal depression. Individual pedicles were enveloped by large Muller cell processes. Long (~5-10 µm) telodendritic processes arose from each pedicle and extended through the matrix of Müller cell processes to contact adjacent pedicles at apparent gap junctions. The foveal pedicles contained 20+ synaptic ribbons in triadic relation to apparent horizontal and bipolar cell processes.

Conclusions : In a single human retina the synaptic outputs of the cones situated at the center of the fovea were not displaced laterally as expected but were localized to the center of the foveal depression. These pedicles formed a distinctivie anatomical relaationship with large Muller cells and postreceptoral processes. We hypothesize that this region may represent a previously unrecognized locus for the circuitry that initiates foveal vision.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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