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Anna Matynia, Eileen Nguyen, Xiaoping Sun, Jason Kessler, Sachin Parikh, Zhe Wang, Luis Perez de Sevilla Muller, Steven Nusinowitz, Steven A Barnes, Nicholas Brecha, Michael B Gorin; Melanopsin expressing neurons are located in the trigeminal ganglia. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4659.
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© ARVO (1962-2015); The Authors (2016-present)
Sensitivity to normal levels of light can negatively impact productivity and quality of life, and is a clinical problem of increasing concern and interest. Previously, we showed melanopsin-expressing ipRGCs mediate innate light and corneal damage-induced light aversion. The current study examines the connection between melanopsin-expressing neurons, and the optic and trigeminal nerves.
Melanopsin expression was analysed by RT-PCR for mRNA and visualized in the OPN4-EGFP reporter strain using confocal laser scanning microscopy. Whole cell patch clamp recordings of dissociated trigeminal neurons with blue light stimulation was used. Light aversion (AI: 0 or negative=no aversion; 1=complete aversion) was used to assess photosensitivity in wild type mice (WT) and mice lacking melanopsin expressing cells (OPN4DTA/DTA), rod and cone photoreceptors (rd1), or mice with a 15s bilateral optic nerve crush (ONC). Nitroglycerin (NTG) was used as a migraine model. Cholera toxin subunit B (CTB) was used for neural tracing.
We detected melanopsin mRNA in trigeminal ganglia and observed GFP fluorescence in approximately 3% of small trigeminal ganglion neurons localized preferentially in the ophthalmic branch. Isolated melanopsin-expressing trigeminal neurons fire action potentials in response to blue light stimulation. NTG increases light aversion even after severe bilateral ONC (AI: ONC=0.46±10.16; WT=0.79±0.09); OPN4dta/dta=0.69±0.08; rd1=0.73±0.04; ONC with vehicle= AI=-0.21±0.07). Neither OPN4dta/dta with ONC (AI=0.19±0.22) or OPN4dta/dta rd1 double mutants (AI=0.12±0.02) showed NTG-induced light aversion. Results with CTB labelling of cornea-projecting trigeminal neurons will be shown.
Melanopsin is expressed in a subset of small trigeminal ganglion neurons, confers intrinsic photosensitivity to these neurons and may contribute to light aversion in a migraine model independently of the optic nerve. Our results demonstrate the possibility of a novel light-pain neural circuit that may provide the first direct mechanism for light-evoked pain.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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