Sensory and sympathetic innervation of the mouse and guinea pig corneal epithelium

Abstract

This study used immunohistochemistry, retrograde tracing, and high-resolution confocal microscopy to explore the structure and neurochemistry of nerve terminals in the corneal epithelium of mice and guinea pigs. In both species, sub-basal nerves formed a plexus in the basal epithelium. Some axons had bulbar endings within the basal epithelium, but most projected perpendicularly from sub-basal nerves to within a few micrometers of the epithelial surface. Three morphologies for these nerve terminals were identified. Simple terminals did not branch after leaving the sub-basal nerves and ended with a single, bulbar swelling. Ramifying terminals branched in the squamous cell layer, forming horizontal fibers that ran parallel to the surface and terminated with single bulbar swellings. Complex terminals branched as they approached the epithelial surface, forming a cluster of highly branched fibers with multiple bulbar endings. Calcitonin gene-related peptide immunolabeled (peptidergic) axons ended mostly in simple terminals, whereas transient receptor potential cation channel subfamily M member 8 immunolabeled (cold receptor) axons ended almost exclusively in complex terminals. Retrograde labeling identified discrete subpopulations of corneal afferent neurons in the trigeminal ganglion. Tyrosine hydroxylase-immunolabeled (sympathetic) nerve terminals originating from the superior cervical ganglion occurred throughout the corneal epithelium of mice, but only in the basal epithelium of guinea pigs. These findings demonstrate that nerve terminals in the corneal epithelium of mice and guinea pigs can be distinguished on the basis of their morphology and neurochemistry, and suggest that nerve terminals with different sensory modalities can be defined on the basis of their morphology.

Functional Properties of Sensory Nerve Terminals of the Mouse Cornea

“…24,33,36 In contrast, the technique used to record from single corneal nerve terminals in vitro in guinea pig or mouse eyes favors the detection of thin cold thermoreceptor terminals, which display spontaneous activity, are more superficially located, and branch more extensively than polymodal and mechanoreceptor endings, thus producing larger-amplitude NTIs. 17,24,[26][27][28]33,34,39,40 In the present work, we tried to confront this caveat through a systematic sampling of impulse activity at regularly distributed points on the corneal surface, thus reaching theoretically all types of nerve terminals. Only terminals that were unambiguously identified were counted.…”

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

“…45 Moreover, corneal polymodal nociceptor axons are sparsely branched, generally with simple or ramifying epithelial endings. 46,47 It is therefore possible that in most cases destruction of polymodal axons by PRK affects most if not all the branches of a parent axon within the epithelium and subepithelium, thus requiring a longer time to regenerate. In contrast, cold thermoreceptor corneal axons branch very extensively and form predominantly complex endings, 24,47 a part of which may be spared from injury, thus facilitating regeneration.…”

“…46,47 It is therefore possible that in most cases destruction of polymodal axons by PRK affects most if not all the branches of a parent axon within the epithelium and subepithelium, thus requiring a longer time to regenerate. In contrast, cold thermoreceptor corneal axons branch very extensively and form predominantly complex endings, 24,47 a part of which may be spared from injury, thus facilitating regeneration. Still, 30 days after PRK, NTI activity of cold thermoreceptor endings within the treated area is often abnormal, suggesting that the recovery of electrophysiological properties at this time is still incomplete.…”

La douleur oculaire chronique : mieux la comprendre pour mieux la traiter

“…Elles se caractérisent par leur forte affinité pour l'isolectine B4 (IB4). La distinction entre populations peptidergique et non peptidergique n'est cependant pas si aisée : les neurones sensoriels du ganglion trigéminal qui lient IB4 contiennent également la SP ou le CGRP [11,12]. Chez la souris, environ 20 % des neurones cornéens sont non peptidergiques (évalué par l'absence de marquage de SP ou de CGRP) [12].…”

“…La distinction entre populations peptidergique et non peptidergique n'est cependant pas si aisée : les neurones sensoriels du ganglion trigéminal qui lient IB4 contiennent également la SP ou le CGRP [11,12]. Chez la souris, environ 20 % des neurones cornéens sont non peptidergiques (évalué par l'absence de marquage de SP ou de CGRP) [12]. Les fibres nerveuses autonomes d'origine sympathique (provenant du ganglion cervical supérieur) expriment la tyrosine hydroxylase, la noradrénaline et/ou le neuropeptide Y (NPY).…”