Harumitsu Hirata1, Mark I Rosenblatt2. 1. Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States Department of Ophthalmology, Weill Cornell Medical College, New York, New York, United States. 2. Department of Ophthalmology, Weill Cornell Medical College, New York, New York, United States.
Abstract
PURPOSE: Tear hyperosmolarity is a ubiquitous feature of dry-eye disease. Although dry-eye patients' sensitivity to cooling is well known, the effects of tear hyperosmolarity on a small amount of cooling in the corneal nerves have not been quantitatively examined. Recently reported corneal afferents, high-threshold cold sensitive plus dry-sensitive (HT-CS + DS) neurons, in rats is normally excited by strong (>4°C) cooling of the cornea, which, when applied to healthy humans, evokes the sensation of discomfort. However, corneal cooling measured between blinks does not exceed 2°C normally. Thus, we sought to determine if these nociceptors could be sensitized by hyperosmolar tears such that they are now activated by small cooling of the ocular surface. METHODS: Trigeminal ganglion neurons innervating the cornea were extracellularly recorded in isoflurane-anesthetized rats. The responses of single corneal neurons to cooling stimuli presented in the presence of hyperosmolar (350-800 mOsm NaCl) tears were examined. RESULTS: The HT-CS + DS neurons with thresholds averaging 4°C cooling responded to cooling stimuli presented after 15 minutes of hyperosmolar tears with thresholds of less than 1°C. The response magnitudes also were enhanced so that the responses to small (2°C) cooling emerged, where none was observed before. CONCLUSIONS: These results demonstrate that after exposure to hyperosmolar tears, these nociceptive corneal neurons now begin to respond to the slight cooling normally encountered between blinks, enabling the painful information to be carried to the brain, which could explain the cooling-evoked discomfort in dry eye patients. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
PURPOSE: Tear hyperosmolarity is a ubiquitous feature of dry-eye disease. Although dry-eyepatients' sensitivity to cooling is well known, the effects of tear hyperosmolarity on a small amount of cooling in the corneal nerves have not been quantitatively examined. Recently reported corneal afferents, high-threshold cold sensitive plus dry-sensitive (HT-CS + DS) neurons, in rats is normally excited by strong (>4°C) cooling of the cornea, which, when applied to healthy humans, evokes the sensation of discomfort. However, corneal cooling measured between blinks does not exceed 2°C normally. Thus, we sought to determine if these nociceptors could be sensitized by hyperosmolar tears such that they are now activated by small cooling of the ocular surface. METHODS: Trigeminal ganglion neurons innervating the cornea were extracellularly recorded in isoflurane-anesthetized rats. The responses of single corneal neurons to cooling stimuli presented in the presence of hyperosmolar (350-800 mOsm NaCl) tears were examined. RESULTS: The HT-CS + DS neurons with thresholds averaging 4°C cooling responded to cooling stimuli presented after 15 minutes of hyperosmolar tears with thresholds of less than 1°C. The response magnitudes also were enhanced so that the responses to small (2°C) cooling emerged, where none was observed before. CONCLUSIONS: These results demonstrate that after exposure to hyperosmolar tears, these nociceptive corneal neurons now begin to respond to the slight cooling normally encountered between blinks, enabling the painful information to be carried to the brain, which could explain the cooling-evoked discomfort in dry eyepatients. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
Authors: Richard J Braun; Nicholas R Gewecke; Carolyn G Begley; P Ewen King-Smith; Javed I Siddique Journal: Invest Ophthalmol Vis Sci Date: 2014-02-26 Impact factor: 4.799
Authors: Jelle Vehof; Diana Kozareva; Pirro G Hysi; Juliette Harris; Ayrun Nessa; Frances K Williams; David L H Bennett; Steve B McMahon; Samantha J Fahy; Kenan Direk; Tim D Spector; Christopher J Hammond Journal: JAMA Ophthalmol Date: 2013-10 Impact factor: 7.389
Authors: Carlos Belmonte; Jason J Nichols; Stephanie M Cox; James A Brock; Carolyn G Begley; David A Bereiter; Darlene A Dartt; Anat Galor; Pedram Hamrah; Jason J Ivanusic; Deborah S Jacobs; Nancy A McNamara; Mark I Rosenblatt; Fiona Stapleton; James S Wolffsohn Journal: Ocul Surf Date: 2017-07-20 Impact factor: 5.033
Authors: Tina B McKay; Yashar Seyed-Razavi; Chiara E Ghezzi; Gabriela Dieckmann; Thomas J F Nieland; Dana M Cairns; Rachel E Pollard; Pedram Hamrah; David L Kaplan Journal: Prog Retin Eye Res Date: 2018-11-16 Impact factor: 21.198