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H. Hirata, I. D. Meng; A Special Type of Primary Afferent Sensory Neuron Plays a Critical Role in Tear Production: Implications for Dry Eye Disease. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4247.
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Although basal tearing has been proposed to be an important factor in the homeostasis of ocular tissues such as cornea, the specific system that drives the production of basal tears is unclear. A previous study (J. Neurosci., 2004, 24:4224) found the existence of a central neural circuit hypothesized to be involved in lacrimation. We now report the existence of a specific type of peripheral sensory neuron that monitors the fluid level of the ocular surface and display properties consistent with their role in the modulation of basal tearing.
Single sensory neurons innervating the cornea were recorded in vivo extracellularly from the trigeminal ganglion of isoflurane-anesthetized rats with tungsten microelectrodes. The ocular surface was kept moist with artificial tears (AT). Neurons were identified by the presence of spontaneous activity and the response to drying of ocular surface. After verifying their receptive field loci on cornea with a cold dental probe, response properties were characterized with a variety of stimuli such as AT, temperature changes (35-15oC), menthol (10-100 uM) and osmotically active solutions (NaCl, sucrose, mannitol), applied to the ocular surface.
1) A specific type of neuron was found that increased their discharge rates when the corneal surface was dried by removing AT with Kimwipe and decreased firings when the cornea was moistened with AT: this is a presumptive negative feedback loop to maintain normal ocular surface fluid status. 2) These neurons displayed the highly sensitive response to cooling (less than 1oC) of cornea as well as a "paradoxical" response to noxious heat (greater than 47oC), and responded to menthol applied to the cornea in a concentration dependent manner, properties consistent with those found in the innocuous "cold" thermoreceptors in the skin of mammals. 3) These neurons increased their discharge rates in response to hypertonic solutions covering the ocular surface, suggesting that increased concentration of solutes caused by evaporation of fluid from the ocular surface may be another adequate stimulus for these neurons.
These innocuous "cold" corneal thermoreceptors were found to respond to drying, cooling and evaporation of cornea consistent with their role in activating the afferent limb of the basal tearing reflex. Dysfunction of these receptors and/or of the neural axis along the lacrimation reflex pathway may be responsible for some forms of dry eye disease. Molecular studies are under way to gain insight into the mechanisms and the properties of these neurons to help discover new avenues for the treatment of dry eye.
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