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Valentina Dallacasagrande, Kamila Mizerska, Harumitsu Hirata, Mark Rosenblatt; Estimating tear osmolarity from the activity of the corneal nerves during corneal dryness (tear evaporation) in rats.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1428.
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Tear hyperosmolarity is thought to play a critical role in the initiation and/or perpetuation of dry eye disease (DED). Therefore, a variety of techniques has been used previously to estimate tear osmolarity in normal and dry eye patients, which resulted in a wide range of osmolarity values. However, no study has addressed this issue through the “eyes” of the corneal nerves. We previously reported that a population of corneal nerves reliably monitors the level of osmolarity around their nerve terminals in epithelia. Thus, we used their activity in an attempt to estimate tear osmolarity during 2-min corneal dryness.
In isoflurane-anesthetized rats, we recorded extracellularly from single trigeminal ganglion neurons innervating the cornea. A population of the corneal nerves that responded preferentially to hyperosmolar solutions (as opposed to cooling) applied to the ocular surface were selectively searched and studied. To determine the extent to which these corneal neurons’ responses to drying of the cornea were induced via the activation by hyperosmolar stimuli, we assessed the responses to ocular instillation of 1) 500 mOsm/L, 2) 600 mOsm/L, and 3) a graded series of hyperosmolar stimuli ranging from 350-1000 mOsm/L.
The maximum magnitudes of the responses during 2-min corneal dryness were matched almost exactly to those induced by the ocular instillation of the 600 mOsm/L stimuli but not by the 500 mOsm/L solutions. The response magnitudes to a graded series of hyperosmolar solutions were nearly linear from the 350 to the 600 mOsm/L stimuli, but reached a plateau or declined slightly thereafter.
Our results demonstrated that tear osmolarity in rats could reach 600-1000 mOsm/L during corneal dryness, consistent with values previously calculated of tears’ osmolarity during tear break-up or thinning. Furthermore, we predict that a spontaneous eye blink could be generated at a tear osmolarity of ~400 mOsm/L if the blink is solely determined by hyperosmolar tears; however, ocular surface cooling can become a major factor also if hyperosmolar tears occurring during evaporation lower the threshold of activation of the neurons.
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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