Elsevier

Experimental Eye Research

Volume 117, December 2013, Pages 79-87
Experimental Eye Research

Review
The role of corneal afferent neurons in regulating tears under normal and dry eye conditions

https://doi.org/10.1016/j.exer.2013.08.011Get rights and content

Highlights

  • Tearing is regulated through a reflex initiated by trigeminal primary afferents.

  • Corneal afferents sense tear film evaporation and potentially damaging stimuli.

  • Dry eye modifies corneal afferents, affecting the regulation of secretions.

Abstract

The cornea is one of several orofacial structures requiring glandular secretion for proper lubrication. Glandular secretion is regulated through a neural reflex initiated by trigeminal primary afferent neurons innervating the corneal epithelium. Corneal sensory afferents must respond to irritating and potentially damaging stimuli, as well as drying that occurs with evaporation of the tear film, and the physiological properties of corneal afferents are consistent with these requirements. Polymodal neurons are sensitive to noxious mechanical, thermal and chemical stimuli, mechanoreceptive neurons are selectively activated by mechanical stimuli, and cool cells respond to innocuous cooling. The central terminations of corneal primary afferents are located within two regions of the spinal trigeminal nucleus. The more rostral region, located at the transition between the trigeminal subnucleus caudalis and interpolaris, represents a critical relay for the regulation of the lacrimation reflex. From this region, major control of lacrimation is carried through projections to preganglionic parasympathetic neurons located in or around the superior salivatory nucleus. Dry eye syndrome may be caused by a dysfunction in the tear secreting glands themselves or in the neuronal circuit regulating these glands. Furthermore, the dry eye condition itself may modify the properties of corneal afferents and affect their ability to regulate secretion, a possibility just now being explored.

Section snippets

Overview

The cornea requires constant secretion from multiple glands to provide lubrication, nourishment and a protective barrier to the external environment (Dartt, 2009). Although the secretory fluids from each gland vary with regards to composition, among the common constituents of glandular secretion are water, electrolytes, mucins, and other glycoproteins and proteins. Sensory innervation of the cornea is necessary to detect environmental stressors and, through brainstem circuits, regulate the flow

Cornea primary afferent neurons

The cornea is the most densely innervated tissue in the body and, based on their conduction velocity, is exclusively innervated by A-delta and C primary afferent fibers (Muller et al., 2003, Zander and Weddell, 1951). Afferent nerve bundles innervating the cornea enter the stroma from the periphery, branching to form a midstromal plexus (Marfurt et al., 2010). Continuing to branch, nerves penetrate Bowman's layer to form the subbasal nerve plexus. In order to maintain the transparency of the

Central processing within the spinal trigeminal nucleus

Trigeminal primary afferent neurons innervating the head and face carry sensory information to Vsp, which is divided into three primary subdivisions: subnucleus oralis (Vo), interpolaris (Vi), and caudalis (Vc), from rostral to caudal (Olszewski, 1950). The processing of sensory information in Vsp is unique from that of the spinal cord dorsal horn in that there are multiple representations of the same orofacial region in different subnuclei of Vsp (Bereiter et al., 2000). As might be expected,

Properties of corneal sensory neurons in dry eye

In vivo confocal microscopy in humans has allowed for the examination of the subbasal nerve plexus in dry eye patients (Cruzat et al., 2010). Results have not been entirely consistent with regards to differences in the overall density of the subbasal plexus, which may be the result of the varying causes and stages of dry eye in these studies. However, an increase in subbasal nerve tortuosities and bead-like formations has been consistently described (Benitez-Del-Castillo et al., 2007, Erdelyi

Future directions

At present, the neural regulation of tearing under normal conditions is relatively well characterized. Noxious mechanical, thermal, and chemical stimuli activate corneal primary afferent polymodal receptors and mechanoreceptors, whereas innocuous cooling, such as that which occurs during minute-to-minute evaporation of the tear film, increases corneal cold receptor activity. These primary afferent neurons project to the Vi/Vc transition region in the brainstem, a critical relay in the

Acknowledgments

Funding was provided by the National Eye Institute R01EY021230 to I.D.M. The authors declare no competing financial interests.

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