July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Integrative and rapid discovery of retinal regulatory molecules
Author Affiliations & Notes
  • Melanie Samuel
    Department of Neuroscience, HCOA, Baylor College of Medicine, Houston, Texas, United States
  • Brian Liu
    Department of Neuroscience, HCOA, Baylor College of Medicine, Houston, Texas, United States
  • Nicholas Albrecht Albrect
    Department of Neuroscience, HCOA, Baylor College of Medicine, Houston, Texas, United States
  • Danye Jiang
    Department of Neuroscience, HCOA, Baylor College of Medicine, Houston, Texas, United States
  • Courtney Burger
    Department of Neuroscience, HCOA, Baylor College of Medicine, Houston, Texas, United States
  • Fenge Li
    Department of Neuroscience, HCOA, Baylor College of Medicine, Houston, Texas, United States
  • Jonathan Alevy
    Department of Neuroscience, HCOA, Baylor College of Medicine, Houston, Texas, United States
  • Julia Wang
    Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States
  • Chih-Wei Hsu
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States
  • Sowmya Kalaga
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States
  • Ritu Bohat
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States
  • Monica Justice
    Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada
  • Shinya Yamamoto
    Jan and Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas, United States
  • John Seavitt
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States
  • Arthur Beaudet
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States
  • Dickinson Mary
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States
  • Footnotes
    Commercial Relationships   Melanie Samuel, None; Brian Liu, None; Nicholas Albrect, None; Danye Jiang, None; Courtney Burger, None; Fenge Li, None; Jonathan Alevy, None; Julia Wang, None; Chih-Wei Hsu, None; Sowmya Kalaga, None; Ritu Bohat, None; Monica Justice, None; Shinya Yamamoto, None; John Seavitt, None; Arthur Beaudet, None; Dickinson Mary, None
  • Footnotes
    Support  NIH 1DP2EY027984 – 01 , NIH 1K99AG044444-01
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2597. doi:
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      Melanie Samuel, Brian Liu, Nicholas Albrecht Albrect, Danye Jiang, Courtney Burger, Fenge Li, Jonathan Alevy, Julia Wang, Chih-Wei Hsu, Sowmya Kalaga, Ritu Bohat, Monica Justice, Shinya Yamamoto, John Seavitt, Arthur Beaudet, Dickinson Mary; Integrative and rapid discovery of retinal regulatory molecules. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2597.

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

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Abstract

Purpose : Retinal neurons relay visual information by forming precise circuits in which hundreds of individual neurons connect with appropriate wiring partners. Despite this remarkable complexity, relatively few genes have been directly linked to retinal circuit organization due to a lack of methods to rapidly identify neural wiring molecules in mammals.

Methods : Here, we report the establishment of a pipeline for the Identification of vascular and Neural integrity Genes by High Throughput screening (INSiGHT). Using this system, we have characterized 90 mutant mouse lines and over 400 individual animals. This approach leverages the resources available through the Knockout Mouse Project (KOMP) and evaluates central components of retina structure, including: 1) gene expression patterns, 2) vessel and cellular topographic patterning, and 3) neuron and synaptic arrangement.

Results : Using this system, we have identified 14 unique genes required for neuronal, neurovascular, and synaptic organization in mouse retina. These genes control distinct aspects of cellular function, with the majority regulating cellular structure, protein transport or function, and gene expression. An interesting subset also regulates neurotransmitter formation or release. The majority of the identified genes are novel, having not previously been implicated as retinal regulatory molecules in mouse nor identified in similar screens in flies and zebrafish.

Conclusions : These data expand the genetic landscape involved in retinal circuit organization. They also provide a road map for continued discovery of mammalian retinal regulators that may aid in the identification and characterization of new retina disease causing alleles.

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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