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Carl F Marfurt, Christopher M Reilly, Shin Ae Park, Christopher J Murphy; Autonomic and Sensory Innervation of the Dog Lacrimal Gland. Invest. Ophthalmol. Vis. Sci. 2014;55(13):54.
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Stimulation of corneal and conjunctival sensory nerves produces reflex tears by activating a brainstem circuit that stimulates lacrimal parasympathetic and sympathetic nerves. Defects in this neural loop can lead to a deficiency in tear secretion and the development of dry eye disease (DED). The canine spontaneous dry eye model has been widely used to study the pathophysiologic mechanisms of DED; however, the functional innervation of the dog lacrimal gland remains to be fully characterized. The purpose of the current study was to investigate the density, distribution, and phenotypic diversity of the normal canine lacrimal gland innervation.
Lacrimal gland samples from five healthy mixed-breed dogs were frozen-sectioned and stained by immunohistochemistry using antisera against neurotubulin (NT, a pan-neuronal marker), vasoactive intestinal polypeptide (VIP, a marker for parasympathetic nerves), tyrosine hydroxylase (TH, a marker for sympathetic nerves), and calcitonin gene-related peptide (CGRP) and substance P (SP) (both markers for sensory nerves).
Tissue sections stained by NT immunohistochemistry revealed a dense and uniform innervation of all gland lobules and revealed intimate associations between nerves and acinar cells, myoepithelial cells, ductal cells, and blood vessels. Serial section observations suggested that greater than 95% of all acini were contacted by NT-IR nerves. The vast majority of lacrimal nerves were autonomic, and VIP-IR and TH-IR nerves were present in roughly equal numbers and rivaled in density and distribution the NT-IR fiber population. CGRP-IR and SP-IR nerves were largely perivascular in nature; however, a few CGRP-IR nerves contacted acinar cells.
The results of this study have demonstrated a uniform, dense and phenotypically diverse innervation of the dog lacrimal gland that is overwhelmingly autonomic in nature. The analogous densities and distributions of VIP-IR and TH-IR nerves suggest collaborative cholinergic and adrenergic mechanisms in the regulation of acinar cell secretory processes. The density of TH-IR sympathetic nerves seen here in the dog is considerably greater than that reported in lacrimal glands of other mammals, including, mouse, rat, and rabbit. It is hoped that the data generated here will provide a baseline of “normal innervation” of the canine lacrimal gland against which observations from dogs with spontaneous DED may be compared.
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