June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Evolutionary Conservation of Photosensory Mechanisms in the Primate Melanopsin Neuron
Author Affiliations & Notes
  • Michael Tri Hoang Do
    F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts, United States
    Neurology, Harvard Medical School, Boston, Massachusetts, United States
  • Andreas Liu
    F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts, United States
    Neurology, Harvard Medical School, Boston, Massachusetts, United States
  • Elliott Scott Milner
    F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts, United States
    Neurology, Harvard Medical School, Boston, Massachusetts, United States
  • Yi-Rong Peng
    University of California Los Angeles, Los Angeles, California, United States
  • Philippe Morquette
    F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts, United States
    Neurology, Harvard Medical School, Boston, Massachusetts, United States
  • Hannah Blume
    F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts, United States
    Neurology, Harvard Medical School, Boston, Massachusetts, United States
  • Michael Charles Brown
    F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts, United States
    Neurology, Harvard Medical School, Boston, Massachusetts, United States
  • Gregory S. Bryman
    F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts, United States
    Neurology, Harvard Medical School, Boston, Massachusetts, United States
  • Alan Joseph Emanuel
    F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts, United States
    Neurology, Harvard Medical School, Boston, Massachusetts, United States
  • Joshua R. Sanes
    Harvard University, Cambridge, Massachusetts, United States
  • Paul D Gamlin
    University of Alabama at Birmingham, Alabama, United States
  • Footnotes
    Commercial Relationships   Michael Tri Do None; Andreas Liu None; Elliott Milner None; Yi-Rong Peng None; Philippe Morquette None; Hannah Blume None; Michael Brown None; Gregory Bryman None; Alan Emanuel None; Joshua Sanes None; Paul Gamlin None
  • Footnotes
    Support  NIH EY023648, NIH EY025555, NIH EY030628, NIH EY025840, NIH EY028633, NIH EY025466, NIH 1U54HD090255, NIH EY012196, Harvard Medical School Department of Neurobiology
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4575 – F0437. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Michael Tri Hoang Do, Andreas Liu, Elliott Scott Milner, Yi-Rong Peng, Philippe Morquette, Hannah Blume, Michael Charles Brown, Gregory S. Bryman, Alan Joseph Emanuel, Joshua R. Sanes, Paul D Gamlin; Evolutionary Conservation of Photosensory Mechanisms in the Primate Melanopsin Neuron. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4575 – F0437.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Mammals sense light for diverse purposes—including perception and the regulation of development, physiology, behavior, mood, and cognition—that require intrinsically photosensitive retinal ganglion cells (ipRGCs). These ocular neurons capture photons with a receptor called melanopsin and send information widely throughout the brain. IpRGCs are evolutionarily conserved, providing an opportunity to compare cell types across ecological niche; indeed, few other retinal output neurons appear to be shared between rodents and primates. Present knowledge indicates that rodent and primate ipRGCs diverge fundamentally in their photosensory mechanisms. However, studies of the latter are few, in large part because their live identification is challenging. We pursue the idea that comparison of rodent and primate ipRGCs will clarify our understanding of how cells are tailored to their tasks.

Methods : We developed an acute, ex vivo method of identifying macaque ipRGCs based on immunotagging of melanopsin’s extracellular domain. We performed patch-clamp electrophysiological recordings from macaque ipRGCs, as well as from mouse ipRGCs that expressed macaque melanopsin in lieu of their own. We delivered a suite of visual stimuli and analyzed responses using biophysical methods. To focus on cell-autonomous mechanisms, we added antagonists of synaptic transmission to the extracellular medium.

Results : Our experiments indicate that N-terminal immunotagging is innocuous for melanopsin function. Using this approach, we observed deep conservation between macaque and mouse ipRGCs, from molecular mechanisms that broaden wavelength sensitivity and response lifetime to cellular mechanisms that generate dynamic range for encoding a breadth of environmental light levels. We found one divergence: While the electrical discharges of mouse ipRGCs are irregular, those of macaque ipRGCs are precisely timed.

Conclusions : It appears that many ipRGC mechanisms for sensing environmental illumination are effective enough to stand across the ~70-million-year separation of mice and macaques. Live immunotagging offers a way to identify cell types for functional analysis, and may be especially useful in the study of species that are unamenable to genetic manipulation.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×