June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
C-terminal phosphorylation of mouse melanopsin regulates the kinetics of a subset of melanopsin mediated behaviors in mice
Author Affiliations & Notes
  • Preethi Somasundaram
    University of Maryland Baltimore County, Halethorpe, Maryland, United States
  • Glenn Wyrick
    Washington State University, Pullman, Washington, United States
  • Diego Baltimore Fernandez
    Johns Hopkins University, Baltimore, Maryland, United States
  • Alireza Ghahari
    National Institute of Health, Bethesda, Maryland, United States
  • Cindy Pinhal
    Washington State University, Pullman, Washington, United States
  • Melissa Simmonds-Richardson
    Johns Hopkins University, Baltimore, Maryland, United States
  • Alan Rupp
    Johns Hopkins University, Baltimore, Maryland, United States
  • Lihong Cui
    National Institute of Mental Health, Bethesda, Maryland, United States
  • Zhijian Wu
    National Institute of Health, Bethesda, Maryland, United States
  • Lane Brown
    Washington State University, Pullman, Washington, United States
  • Tudor C. Badea
    National Institute of Health, Bethesda, Maryland, United States
  • Samer Hattar
    Johns Hopkins University, Baltimore, Maryland, United States
  • Phyllis Robinson
    University of Maryland Baltimore County, Halethorpe, Maryland, United States
  • Footnotes
    Commercial Relationships   Preethi Somasundaram, None; Glenn Wyrick, None; Diego Fernandez, None; Alireza Ghahari, None; Cindy Pinhal, None; Melissa Simmonds-Richardson, None; Alan Rupp, None; Lihong Cui, None; Zhijian Wu, None; Lane Brown, None; Tudor Badea, None; Samer Hattar, None; Phyllis Robinson, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4129. doi:
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      Preethi Somasundaram, Glenn Wyrick, Diego Baltimore Fernandez, Alireza Ghahari, Cindy Pinhal, Melissa Simmonds-Richardson, Alan Rupp, Lihong Cui, Zhijian Wu, Lane Brown, Tudor C. Badea, Samer Hattar, Phyllis Robinson; C-terminal phosphorylation of mouse melanopsin regulates the kinetics of a subset of melanopsin mediated behaviors in mice
      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):4129.

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

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Abstract

Purpose : Melanopsin is a visual pigment, expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs) of the mammalian retina, that plays a major role in non-image forming visual behaviors like the pupillary light reflex, circadian photoentrainment, and sleep. It is hypothesized that melanopsin mediated phototransduction is terminated by the phosphorylation of melanopsin’s C-terminus by a G-protein coupled receptor kinase, followed by b-arrestin binding. Little is known about the contribution of melanopsin phosphorylation to ipRGC physiology and its influence on non-image forming behaviors. We investigated the role of melanopsin C-terminus phosphorylation on non-image forming behaviors by generating a phosphorylation deficient melanopsin mutant that lacks all putative C-terminal phosphorylation sites (C-phosphonull).

Methods : C-phosphonull mice were generated by expressing the C-terminal phosphorylation deficient melanopsin mutant in Opn4Cre/Cre mice by intravitreal delivery of an AAV2 construct for targeted expression of melanopsin in ipRGCs.

Results : We found that C-terminal phosphorylation of melanopsin has a direct influence on the dilation kinetics of the pupillary light reflex, due to the observation that the C-phosphonull mice exhibit prolonged pupil constriction to a high intensity blue light stimulus, and have a half time of dilation of 9.43min as compared to only 6s in wildtype animals. This phenotype is reflected in the physiology of ipRGCs as determined by both single cell and multielectrode recordings, where ipRGCs sustain action potentials for atleast 15min to a 5s blue light stimulus. We also found that exogenous expression of melanopsin in melanopsin knockout animals enhances their ability to shift their activities to a delayed light dark cycle (a jet lag paradigm) and rescues a deficit in negative masking (reduction in activity exhibited by nocturnal animals in response to aberrant light during subjective night).

Conclusions : Our results suggest that C-terminal phosphorylation of melanopsin influences the kinetics of some non-image forming behaviors and physiology, but does not completely explain deactivation of melanopsin and that there may be alternate mechanisms that play a role in its absence.

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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