July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
A Pathoconnectome of Early Retinal Remodeling
Author Affiliations & Notes
  • Rebecca Pfeiffer
    Moran Eye Center/ Ophthalmology, University of Utah, Salt Lake City, Utah, United States
  • Robert E Marc
    Moran Eye Center/ Ophthalmology, University of Utah, Salt Lake City, Utah, United States
  • James R. Anderson
    Moran Eye Center/ Ophthalmology, University of Utah, Salt Lake City, Utah, United States
  • Daniel P Emrich
    Moran Eye Center/ Ophthalmology, University of Utah, Salt Lake City, Utah, United States
  • Carl B Watt
    Moran Eye Center/ Ophthalmology, University of Utah, Salt Lake City, Utah, United States
  • Jia-Hui Yang
    Moran Eye Center/ Ophthalmology, University of Utah, Salt Lake City, Utah, United States
  • Kevin D Rapp
    Moran Eye Center/ Ophthalmology, University of Utah, Salt Lake City, Utah, United States
  • Jeebika Dahal
    Moran Eye Center/ Ophthalmology, University of Utah, Salt Lake City, Utah, United States
  • Mineo Kondo
    Mie University, Tsu, Japan
  • Hiroko Terasaki
    Nagoya University, Nagoya-shi, Japan
  • Bryan W. Jones
    Moran Eye Center/ Ophthalmology, University of Utah, Salt Lake City, Utah, United States
  • Footnotes
    Commercial Relationships   Rebecca Pfeiffer, None; Robert Marc, Signature Immunologics (I); James Anderson, None; Daniel Emrich, None; Carl Watt, None; Jia-Hui Yang, None; Kevin Rapp, None; Jeebika Dahal, None; Mineo Kondo, None; Hiroko Terasaki, None; Bryan Jones, None
  • Footnotes
    Support  NIH Grant EY015128, NIH Grant EY014800, RPB (unrestricted grant to the Moran Eye Center)
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5990. doi:
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    • Get Citation

      Rebecca Pfeiffer, Robert E Marc, James R. Anderson, Daniel P Emrich, Carl B Watt, Jia-Hui Yang, Kevin D Rapp, Jeebika Dahal, Mineo Kondo, Hiroko Terasaki, Bryan W. Jones; A Pathoconnectome of Early Retinal Remodeling. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5990.

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

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Abstract

Purpose : Retinal remodeling is a consequence of retinal degenerative disease, during which neurons sprout new neurites whose synaptic structures and partners are not yet defined. Simultaneously during remodeling, Müller cells (MCs) undergo structural and metabolic changes, whose impact on surrounding neurons is an active area of research. Retinal connectomes have elucidated and validated fundamental networks. These data provide further classification of neuronal types and subtypes and a precise framework for modeling of retinal function, based on ground truth networks. The creation of the first pathoconnectome (RPC1), a connectome from pathological retinal tissue, provides the opportunity to determine connectivites between neurons, while simultaneously evaluating glial remodeling. Computational Molecular Phenotyping (CMP) embedded within the ultrastructure provides metabolic factors of pathologies.

Methods : RPC1 was collected post-mortem from a 10mo TgP347L rabbit model of adRP, fixed in 1% FA, 2.5% GA, 3% sucrose, and 1mM MgSO4 in cacodylate buffer (pH 7.4). The tissue was osmicated, dehydrated, resin embedded, and sectioned at 70nm. Sections were placed on formvar grids, stained, and imaged on a JEOL JEM-1400 TEM using SerialEM. 1 section was reserved from every 30 section for CMP, where it was probed for small molecules: glutamate, glutamine, glycine, GABA, taurine, glutathione; or proteins GFAP and GS. RPC1 was evaluated using the Viking software suite.

Results : RPC1 was chosen based on early features of retinal degeneration/remodeling: degeneration of rod OS, MC hypertrophy, and neuronal sprouting. RPC1 consists of 948 serial sections spanning the ONL to the vitreous, with a diameter of 90µm. We find dendrites extending from rod bipolar cells to cone pedicles, originally described in light microscopy, and active synaptic contacts. We also see alterations of synaptic structure in the IPL, and MC morphological changes affecting surface to volume and neuron/glial relationships. Network motifs are being actively investigated.

Conclusions : We observe many features of remodeling previously described using light microscopy, and confirm active synaptic contact. We also find synaptic structural features, not previously described. In addition, early evaluation of MC morphology demonstrates marked changes in MC shape and associations with nearby neurons and glia, which, combined with CMP, will be instrumental in understanding how MCs affect retinal remodeling.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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