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C.F. Marfurt, L. Dvorscak; Peptidergic and Non–Peptidergic Innervation of the Rat Cornea . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2724.
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Corneal sensory nerves are neurochemically diverse and organized into two broad groups. Fibers in the first group contain neuropeptides such as CGRP and SP and depend on nerve growth factor (NGF) for their postnatal survival. Fibers in the second group are largely non–peptidergic, express a cell–surface glycoconjugate that binds the plant isolectin B4 (IB4+), and likely depend on glial cell line–derived neurotrophic factor (GDNF) for their postnatal survival. Previous work by Silverman and Kruger (1988) have shown that IB4+ fibers are abundantly distributed in the rat cornea; however, the contribution that these nerves make to the total corneal innervation is not known. The purpose of this study is to determine the percentages of rat corneal neurons that are IB4–positive, CGRP–positive, or both.
In the first set of experiments, corneal afferent neurons in 8 trigeminal ganglia were labeled by the retrograde transport of wheat germ agglutinin (WGA) from the scarified central cornea. Two days later, the animals were perfusion–fixed and alternate sections through the ipsilateral trigeminal ganglia were processed immunohistochemically for the presence of WGA and either IB4 or CGRP. In a separate set of 4 animals, the percentages of trigeminal ganglia neurons in the ophthalmo–maxillary region that were IB4+ and also contained either CGRP or galanin were determined.
A total of 767 corneal afferent neurons were labeled with WGA and of these 45.7% were IB4+ and 31.0% were CGRP+. Double–labeling of IB4+ neurons in the ophthalmo–maxillary region revealed that only 9.2% (53/575) and 2.2% (18/801) of IB4+ neurons contained CGRP or galanin, respectively.
Almost one–half of rat corneal sensory neurons are IB4+, while approximately one–third contain CGRP. Although small percentages of trigeminal ganglion IB4+ neurons express CGRP or galanin, the data support the hypothesis that the cornea is innervated by two phenotypically–distinct populations of nociceptive neurons: peptidergic and IB4+ ("peptide–poor"). The neurochemical signature of most IB4+ neurons remains largely unknown. Given the high percentage of corneal nerves that are IB4+, further study of the response properties, trophic functions, and regenerative capacity of this robust fiber population seems warranted.
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