April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Circuitry Of Light-associated Allodynia
Author Affiliations & Notes
  • Anna Matynia
    Dept of Ophthalmology, Jules Stein Eye Institute - UCLA, Los Angeles, California
  • Sachin Parikh
    Dept of Ophthalmology, Jules Stein Eye Institute - UCLA, Los Angeles, California
  • Michael B. Gorin
    Dept of Ophthalmology, Jules Stein Eye Institute - UCLA, Los Angeles, California
  • Footnotes
    Commercial Relationships  Anna Matynia, None; Sachin Parikh, None; Michael B. Gorin, None
  • Footnotes
    Support  Oppenheimer Endowment Award 2009-2010 to MBG and AM. Harold and Pauline Price Chair in Ophthalmology and the Jules Stein Eye Institute to MBG
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 3468. doi:
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      Anna Matynia, Sachin Parikh, Michael B. Gorin; Circuitry Of Light-associated Allodynia. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3468.

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

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Purpose: : Light sensitivity is a clinical problem of increasing concern and interest. As many as 50% of mild traumatic brain injury patients, 75% of migraine patients and many patients with ocular inflammation or cone dysfunction experience light-associated allodynia (LAA), a painful response to normal light. Our studies examine the molecular and neural circuits involved in light aversion using mouse models of LAA.

Methods: : We have developed a light aversion behavioral test to model LAA and have used mutant mice lacking specific components of the retinal circuitry. We have discovered and validated a novel, acute, atraumatic model of severe LAA using low dose opiates. We are using immunohistochemistry to localize opiate receptors with respect to the retinal circuitry that is required for opiate-dependent LAA.

Results: : Previously, we showed that LAA is not dependent on rod or cone input or alternative opsins since mutants lacking functional cones (Gnat2-/-, n=6 and Cnga3-/-, n=7) , rods (Gnat1-/-, n=10), Rrg-/- (n=6) or Rrh-/- (n=13) show normal light aversion. Mice lacking melanopsin-positive, intrinsically photosensitive retinal ganglion cells (ipRGCs) show normal light aversion at lower light levels (0-2000 lux). Since loss of ipRGCs renders these mice unable to constrict their pupils and increases retinal illuminance, we repeated testing after pupillary dilation with atropine of both mutants and wild type littermates. The ipRGC-ablated mice show the same level of light aversion with or without atropine but their wild type littermates show increased aversion with atropine. These mutants and the mice with homozygous deletions of Gnat1, Gnat2, Cnga3, Rgr or Rrh, show enhanced light sensitivity to low-dose morphine. We have optimized illumination levels and morphine doses in this acute model of LAA, have used subunit specific opiate antagonists to confirm the role of the mu opiate receptor.

Conclusions: : We have established that neither RGR-, RRH-opsin, rod nor cone photoreceptors are required for LAA behavior. Current testing with Rpe65 mutants and Pde6b (rd1) mutants will allow us to assess image-forming visual pathway and differentiate between non-functional photoreceptors versus cellular loss of these cells. ipRGCs seem to be critical for integration of light detection from both photoreceptors and melanopsin, and coordinate aversion behavior via activation of the appropriate brain nuclei. A secondary bypass system is likely activated by sub-analgesic exogenous opiate agonists acting either locally on retinal neurons and/or within the central nervous system.

Keywords: retinal connections, networks, circuitry • ganglion cells • photoreceptors: visual performance 

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