Abnormal activity of corneal cold thermoreceptors underlies the unpleasant sensations in dry eye disease

Abstract

Discomfort in dry eye is possibly caused by an augmented ongoing activity in corneal cold neurons secondary to dryness-induced alterations in sodium and potassium channel expression.

Functional and Morphologic Alterations in Mechanical, Polymodal, and Cold Sensory Nerve Fibers of the Cornea Following Photorefractive Keratectomy

“…55 Corneal cold thermoreceptor fibers are implicated in the regulation of basal tearing rate and have been proposed also as the source of the unpleasant dryness sensation associated with dry eye disease. 13,20,24,26 The differences in time course and characteristics of disturbances in corneal nerve activity observed in mice after PRK confirm the important role played by aberrant impulse activity in axotomized nerves for the appearance of dysesthesias following PRK 56 and lend support to the proposal that, among the different functional subclasses of corneal nerves, cold thermoreceptors are major players in the development of phantom unpleasant dryness sensation after photorefractive surgery procedures.…”

“…24 In brief, mice were killed by cervical dislocation and eyes were excised and placed in a physiological saline solution similar to tear fluid (in mM: NaCl [128], KCl [5], NaH 2 PO 4 [1], NaHCO 3 [26], CaCl 2 [2.4], MgCl 2 [1.3], and glucose [10]) and bubbled with carbogen gas (5% CO 2 and 95% O 2 ). The eye was then placed in a recording chamber and was continuously superfused with the same physiological saline solution.…”

“…Excitation of both types of nociceptor fibers elicits reflex blinking and irritative tearing. 13,25 In contrast, cold thermoreceptors mediate sensations of ocular surface cooling and drying 22,26 and play an important role in the modulation of basal tearing and blinking rates associated with the homeostasis of eye surface wetness. 24,27 Surgical injury acutely affects the different classes of sensory axons innervating the ocular surface.…”

The effect of ageing on the ocular surface parameters

“…Previous studies have already shown the lack of association between DED symptoms and ocular surface signs [51] and age [52]. Reduction of the tear secretion in dry eye patients induce inflammation and peripheral nerve damage [53].…”

Functional Properties of Sensory Nerve Terminals of the Mouse Cornea

“…9,[17][18][19] Electrophysiological experiments in other species (cat, rabbit, guinea pig, rat) firmly established that the cornea is functionally innervated by the peripheral axons of three distinct classes of peripheral sensory receptor neurons: mechanosensory, responding only to mechanical forces; polymodal nociceptor, activated by mechanical stimuli as well as heat and a variety of endogenous and exogenous chemicals; and cold thermoreceptor neurons, primarily excited by moderate cooling and hyperosmolar solutions. [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] In the present work, we performed a systematic analysis of the firing properties of the various functional classes of sensory nerve terminals innervating the adult mouse cornea and defined their functional properties and firing pattern in response to stimuli of differing modality.…”