Acute corneal epithelial debridement unmasks the corneal stromal nerve responses to ocular stimulation in rats: implications for abnormal sensations of the eye

Abstract

It is widely accepted that the mechanisms for transducing sensory information reside in the nerve terminals. Occasionally, however, studies have appeared demonstrating that similar mechanisms may exist in the axon to which these terminals are connected. We examined this issue in the cornea, where nerve terminals in the epithelial cell layers are easily accessible for debridement, leaving the underlying stromal (axonal) nerves undisturbed. In isoflurane-anesthetized rats, we recorded extracellularly from single trigeminal ganglion neurons innervating the cornea that are excited by ocular dryness and cooling: low-threshold (<2°C cooling) and high-threshold (>2°C) cold-sensitive plus dry-sensitive neurons playing possible roles in tearing and ocular pain. We found that the responses in both types of neurons to dryness, wetness, and menthol stimuli were effectively abolished by the debridement, indicating that their transduction mechanisms lie in the nerve terminals. However, some responses to the cold, heat, and hyperosmolar stimuli in low-threshold cold-sensitive plus dry-sensitive neurons still remained. Surprisingly, the responses to heat in approximately half of the neurons were augmented after the debridement. We were also able to evoke these residual responses and follow the trajectory of the stromal nerves, which we subsequently confirmed histologically. The residual responses always disappeared when the stromal nerves were cut at the limbus, suggesting that the additional transduction mechanisms for these sensory modalities originated most likely in stromal nerves. The functional significance of these residual and enhanced responses from stromal nerves may be related to the abnormal sensations observed in ocular disease. In addition to the traditional view that the sensory transduction mechanisms exist in the nerve terminals, we report here that the proximal axons (stromal nerves in the cornea from which these nerve terminals originate) may also be capable of transducing sensory information. We arrived at this conclusion by removing the epithelial cell layers of the cornea in which the nerve terminals reside but leaving the underlying stromal nerves undisturbed.

Acute Hyperalgesia and Delayed Dry Eye After Corneal Abrasion Injury

“…Changes in corneal nerve morphology, including swellings, have been reported after both nerve injury and application of intense stimuli such as high osmotic concentrations of hypertonic saline [23 ; 28] suggesting that these enlargements may be a site for aberrant nerve activity. In contrast, responses to stimuli confined to the denervated central cornea are impaired in the hours immediately after heptanol abrasion [27].…”

Acute hyperalgesia and delayed dry eye after corneal abrasion injury

“…By contrast, responses to stimuli confined to the denervated central cornea are impaired in the hours immediately after heptanol abrasion. 28 …”

Morphological and Functional Changes of Corneal Nerves and Their Contribution to Peripheral and Central Sensory Abnormalities

“…Single corneal nerve terminals and ciliary nerve fiber activity recordings are the two main experimental approaches currently reported to evaluate the functional changes of ongoing or evoked nerve activity in fundamental studies. Single unit extracellular recordings to evaluate polymodal and cold-sensitive corneal nerve terminals have been described using ex vivo isolated corneas in mice and in guinea pigs (Acosta et al, 2013 , 2014 ; Kovacs et al, 2016b ; Gonzalez-Gonzalez et al, 2017 ; Hirata et al, 2017 ; Alamri et al, 2018 ; Pina et al, 2019 ).…”