July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Aii Amacrine Cell Connectivity in Degenerating Retina
Author Affiliations & Notes
  • Jeebika Dahal
    Ophthalmology , Moran Eye Center University of Utah, Salt Lake City, Utah, United States
  • Rebecca L Pfeiffer
    Ophthalmology , Moran Eye Center University of Utah, Salt Lake City, Utah, United States
  • Crystal Sigulinsky
    Ophthalmology , Moran Eye Center University of Utah, Salt Lake City, Utah, United States
  • James Anderson
    Ophthalmology , Moran Eye Center University of Utah, Salt Lake City, Utah, United States
  • Daniel Emrich
    Ophthalmology , Moran Eye Center University of Utah, Salt Lake City, Utah, United States
  • Hope Morrison
    Ophthalmology , Moran Eye Center University of Utah, Salt Lake City, Utah, United States
  • Jessica Garcia
    Ophthalmology , Moran Eye Center University of Utah, Salt Lake City, Utah, United States
  • Kevin Rapp
    Ophthalmology , Moran Eye Center University of Utah, Salt Lake City, Utah, United States
  • Jia-Hui Yang
    Ophthalmology , Moran Eye Center University of Utah, Salt Lake City, Utah, United States
  • Carl Watt
    Ophthalmology , Moran Eye Center University of Utah, Salt Lake City, Utah, United States
  • Mineo Kondo
    Ophthalmology, Graduate School of Med Mie University, Tsu, Japan
  • Hiroko Terasaki
    Ophthalmology, School of Medicine Nagoya University, Nagoya-shi, Japan
  • Robert Marc
    Ophthalmology , Moran Eye Center University of Utah, Salt Lake City, Utah, United States
  • Bryan W Jones
    Ophthalmology , Moran Eye Center University of Utah, Salt Lake City, Utah, United States
  • Footnotes
    Commercial Relationships   Jeebika Dahal, None; Rebecca Pfeiffer, None; Crystal Sigulinsky, None; James Anderson, None; Daniel Emrich, None; Hope Morrison, None; Jessica Garcia, None; Kevin Rapp, None; Jia-Hui Yang, None; Carl Watt, None; Mineo Kondo, None; Hiroko Terasaki, None; Robert Marc, Signature Immunologics (I); Bryan Jones, None
  • Footnotes
    Support  R01 Grant EY015128, R01 Grant EY02576, T32 Grant EY024234, P30 Grant EY014800, Undergraduate research awards from the Undergraduate Research Opportunities Program at the University of Utah, Unrestricted Grant from Research to Prevent Blindness to the Department of Ophthalmology & Visual Sciences
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 551. doi:https://doi.org/
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      Jeebika Dahal, Rebecca L Pfeiffer, Crystal Sigulinsky, James Anderson, Daniel Emrich, Hope Morrison, Jessica Garcia, Kevin Rapp, Jia-Hui Yang, Carl Watt, Mineo Kondo, Hiroko Terasaki, Robert Marc, Bryan W Jones; Aii Amacrine Cell Connectivity in Degenerating Retina. Invest. Ophthalmol. Vis. Sci. 2019;60(9):551. doi: https://doi.org/.

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

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Abstract

Purpose : Aii amacrine cells (Aii ACs) function in mediating scotopic vision via connection of rod bipolar cells (Rod BCs) to cone bipolar cell pathways. The purpose of this project is to determine the effect of retinal degeneration (RD) on Aii AC networks. We explore this in a pathoconnectome of early RD (RPC1), using a connectome of healthy retina (RC1) as control. Cells in each volume are evaluated by comparison of morphology, synaptic connectivity, and eventually network analysis.

Methods : Tissue for RPC1 was collected from a 10 month old transgenic p347L rabbit model of autosomal dominant retinitis pigmentosa. RC1 was collected from a 13 month old Dutch-Belted rabbit, with no indications of degeneration. Tissue was fixed in a mixed aldehyde solution, before subsequent dehydration, osmication, and resin embedding. Volumes were sectioned at 70nm (RPC1) and 90nm (RC1) and placed on formvar grids. 1 section was reserved from every 30 TEM sections for computational molecular phenotyping where it was placed on a slide and probed for small molecules or proteins. TEM sections were captured at 2.18nm/px using SerialEM software on a JEOL JEM-1400 TEM. The RC1 volume has a diameter of 250µm and RPC1 has a diameter of 90µm. Both volumes were analyzed using the Viking software suite.

Results : In this study, Aii ACs from RPC1 were compared to RC1. Initial results indicate no distinct difference in the morphology other than arbor size, which are likely due to eccentricity differences between volumes. However, in RPC1, we observe multiple instances of Aii AC coupling with Rod BCs in the ON region of the IPL. In contrast, Rod BCs never form gap junctions in healthy retina.

Conclusions : Coupling between Aii ACs and Rod BCs in RPC1 is a unique change in retinal network topology occurring in early RD. Further exploration of network changes as a response to RD is warranted, as many therapeutic interventions currently in development rely upon maintenance of inner retinal circuitry. Prior research demonstrates Rod BCs extend dendrites towards cones and change their receptor expression as rods degenerate. Therefore, knowing the network changes involving Aii ACs and their associations with bipolar cells is crucial to understanding how photoreceptor degeneration affects inner retinal visual processing.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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