title: Peripheral Sensory Neurons Expressing Melanopsin Respond to Light.
abstract: The ability of light to cause pain is paradoxical. The retina detects light but is devoid of nociceptors while the trigeminal sensory ganglia (TG) contain nociceptors but not photoreceptors. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are thought to mediate light-induced pain but recent evidence raises the possibility of an alternative light responsive pathway independent of the retina and optic nerve. Here, we show that melanopsin is expressed in both human and mouse TG neurons. In mice, they represent 3% of small TG neurons that are preferentially localized in the ophthalmic branch of the trigeminal nerve and are likely nociceptive C fibers and high-threshold mechanoreceptor Aδ fibers based on a strong size-function association. These isolated neurons respond to blue light stimuli with a delayed onset and sustained firing, similar to the melanopsin-dependent intrinsic photosensitivity observed in ipRGCs. Mice with severe bilateral optic nerve crush exhibit no light-induced responses including behavioral light aversion until treated with nitroglycerin, an inducer of migraine in people and migraine-like symptoms in mice. With nitroglycerin, these same mice with optic nerve crush exhibit significant light aversion. Furthermore, this retained light aversion remains dependent on melanopsin-expressing neurons. Our results demonstrate a novel light-responsive neural function independent of the optic nerve that may originate in the peripheral nervous system to provide the first direct mechanism for an alternative light detection pathway that influences motivated behavior.
authors: Department of Ophthalmology, Jules Stein Eye Institute, David Geffen School of Medicine, UCLALos Angeles, CA, USA; Brain Research Institute, UCLALos Angeles, CA, USA.
authors: Anna
authors: A
authors: Matynia
authors: Department of Ophthalmology, Jules Stein Eye Institute, David Geffen School of Medicine, UCLA Los Angeles, CA, USA.
authors: Eileen
authors: E
authors: Nguyen
authors: Department of Neurobiology and Medicine, David Geffen School of Medicine, UCLA Los Angeles, CA, USA.
authors: Xiaoping
authors: X
authors: Sun
authors: Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University Lund, Sweden.
authors: Frank W
authors: FW
authors: Blixt
authors: Department of Ophthalmology, Jules Stein Eye Institute, David Geffen School of Medicine, UCLALos Angeles, CA, USA; Brain Research Institute, UCLALos Angeles, CA, USA.
authors: Sachin
authors: S
authors: Parikh
authors: Department of Ophthalmology, Jules Stein Eye Institute, David Geffen School of Medicine, UCLA Los Angeles, CA, USA.
authors: Jason
authors: J
authors: Kessler
authors: Department of Neurobiology and Medicine, David Geffen School of Medicine, UCLA Los Angeles, CA, USA.
authors: Luis
authors: L
authors: Pérez de Sevilla Müller
authors: Department of Ophthalmology, Jules Stein Eye Institute, David Geffen School of Medicine, UCLA Los Angeles, CA, USA.
authors: Samer
authors: S
authors: Habib
authors: Department of Ophthalmology, Jules Stein Eye Institute, David Geffen School of Medicine, UCLA Los Angeles, CA, USA.
authors: Paul
authors: P
authors: Kim
authors: Department of Ophthalmology, Jules Stein Eye Institute, David Geffen School of Medicine, UCLA Los Angeles, CA, USA.
authors: Zhe Z
authors: ZZ
authors: Wang
authors: Department of Neurobiology and Medicine, David Geffen School of Medicine, UCLA Los Angeles, CA, USA.
authors: Allen
authors: A
authors: Rodriguez
authors: Brain Research Institute, UCLALos Angeles, CA, USA; Department of Neurology, David Geffen School of Medicine, UCLALos Angeles, CA, USA.
authors: Andrew
authors: A
authors: Charles
authors: Department of Ophthalmology, Jules Stein Eye Institute, David Geffen School of Medicine, UCLA Los Angeles, CA, USA.
authors: Steven
authors: S
authors: Nusinowitz
authors: Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University Lund, Sweden.
authors: Lars
authors: L
authors: Edvinsson
authors: Department of Neurobiology and Medicine, David Geffen School of Medicine, UCLALos Angeles, CA, USA; Departments of Physiology & Biophysics and Ophthalmology and Visual Sciences, Dalhousie UniversityHalifax, NS, Canada.
authors: Steven
authors: S
authors: Barnes
authors: Brain Research Institute, UCLALos Angeles, CA, USA; Department of Neurobiology and Medicine, David Geffen School of Medicine, UCLALos Angeles, CA, USA; Veterans Administration Greater Los Angeles Health SystemLos Angeles, CA, USA.
authors: Nicholas C
authors: NC
authors: Brecha
authors: Department of Ophthalmology, Jules Stein Eye Institute, David Geffen School of Medicine, UCLALos Angeles, CA, USA; Brain Research Institute, UCLALos Angeles, CA, USA.
authors: Michael B
authors: MB
authors: Gorin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008881:Migraine Disorders / Q000378:metabolism / Q000503:physiopathology*; D020221:Optic Nerve Injuries / Q000378:metabolism / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000502:physiology*; D017299:Rod Opsins / Q000378:metabolism / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000378:metabolism / Q000502:physiology*; D000099210:Melanopsin
chemical_list: D017299:Rod Opsins; D000099210:Melanopsin
keywords: choroid; cornea; ipRGC; migraine; optic nerve injury; sensory ganglion