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Harumitsu Hirata, Michael Oshinsky, Nathan Fried; Short exposure to intense tear hyperosmolarity leads to functional alterations of the corneal nerves involved in tearing and/or ocular pain: Implications for dry eye disease. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2193.
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The anterior eye encounters great variations in humidity and temperature in different atmospheric conditions such as desert and arctic environments that likely produce extreme hyperosmolar stress to the cornea. Two methods could be advanced to study the effects of hyperosmolar stress on the corneal nerves. One is to follow the low dose over days or week, and the other is to apply extremely high level for a short period (min-hour). This study investigated the short-term effects of hyperosmolar stress on the corneal functions.
In isoflurane-anesthetized rats, single extracellular recordings were made from trigeminal ganglion while the cornea was stimulated with hyperosmolar NaCl solutions, ocular dryness and temperature changes. The corneal neurons excited by drying of the cornea (dry-sensitive corneal afferents) were studied.
One population of dry-sensitive corneal afferents that were also sensitive to small temperature decrease of the corneal surface was greatly affected by the extreme hyperosmolar stress (1000 mOsm NaCl solutions) that was applied to ocular surface for only 30 min. Their responses to drying of the cornea, a stimulus thought to be critical for production of the tears, were significantly decreased or even silenced after 30 min of hyperosmolar stress that lasted for at least 3 hrs under the same conditions. Their responses to temperature changes of the cornea (19oC cooling and 13oC heating), on the other hand, were greatly enhanced by the hyperosmolar stress after a 15 min ocular application of 800-1000 mOsm NaCl solutions. These changes in excitability of these neurons were not often reversed 15-30 min after replacing the hyperosmolar tears with the normal (~300 mOsm) tears.
A theoretical model predicted that small spots on the corneal surface contain hyperosmolar tears as high as 900 mOsm during the tear breakup. If this were confirmed experimentally, our results suggest that short period of these extreme hyperosmolar conditions of the eye is expected to produce immeasurably grave consequence on the functions of the corneal nerves responsible for tearing and ocular pain sensation. Our results, thus, demonstrate the importance of these extreme conditions in induction of early stages of dry eye disease.
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