Corneal nerve fibers exert trophic effects on the corneal epithelium, regulate epithelial ion transport processes, and influence epithelial mitogenesis and corneal wound healing. The mechanism by which corneal innervation exerts these influences is unknown, but axonally transported substances, possibly neuropeptides, may be involved.
The aims of the current study are to investigate in detail the origins, density, fine structure, and neuropeptide content of the corneal sensory and sympathetic innervations, and to investigate the role of corneal neuropeptides on epithelial mitogenesis and corneal wound healing. Eight types of experiments will be performed in the current study. First, the distribution, numbers, and somata diameters of corneal afferent and efferent neurons in 5 different species will be investigated by the method o? retrograde transport of horseradi peroxidase-wheat germ agglutinin (HRP-WGA). Second, the fine structure and postsynaptic relationships of rat corneal sensory fibers, and rabbit and cat sympathetic fibers, will be studied at the electron microscopic level by labeling the fibers with HRP-WGA transported anterogradely from the trigeminal and superior cervical ganglia. Third the overall densities of the corneal adrenergic Innervations in 5 species will be determined by applying glyoxylic acid-induced fluorescence techniques to the study of split corneal whole mount preparations- Fourth, the brainstem termination sites of rabbit corneal afferent neurons will be investigated by using the method of transganglionic transport of HRP-WGA. In the fifth and sixth sets of experiments, the neuropeptide content of the rat and rabbit corneal innervation will be studied by using immunohistochemical techniques designed to detect the presence of substance P, calcitonin gene-related peptide, cholecystokinin, somatostatin, leucine enkephalin, and neuropeptide Y. In the seventh se of experiments, we will test the ability o? topically applied neuropeptides to alter the rate of epithelial mitogenesis and, in the final set of experiments, we will study the wound healing potential of different neuropeptides or combinations of neuropeptides on three kinds of: standardized, non-penetrating corneal lesions. The long term objectives of the current application are to increase our understanding of the efferent (nonsensory) functions o? the corneal innervations, and to learn if biologically active substances produced and transported in corneal nerves may be used therapeutically to stimulate corneal repair following eye injuries and, perhaps, corneal transplantations.

National Institute of Health (NIH)
National Eye Institute (NEI)
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Visual Sciences A Study Section (VISA)
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Indiana University-Purdue University at Indianapolis
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United States
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Marfurt, C F; Ellis, L C (1993) Immunohistochemical localization of tyrosine hydroxylase in corneal nerves. J Comp Neurol 336:517-31
Marfurt, C F; Ellis, L C; Jones, M A (1993) Sensory and sympathetic nerve sprouting in the rat cornea following neonatal administration of capsaicin. Somatosens Mot Res 10:377-98
Jones, M A; Marfurt, C F (1991) Calcitonin gene-related peptide and corneal innervation: a developmental study in the rat. J Comp Neurol 313:132-50
Marfurt, C F; Echtenkamp, S F (1991) Sensory innervation of the rat kidney and ureter as revealed by the anterograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) from dorsal root ganglia. J Comp Neurol 311:389-404
Keller, J T; Marfurt, C F (1991) Peptidergic and serotoninergic innervation of the rat dura mater. J Comp Neurol 309:515-34
Marfurt, C F; Rajchert, D M (1991) Trigeminal primary afferent projections to ""non-trigeminal"" areas of the rat central nervous system. J Comp Neurol 303:489-511
Kingsley, R E; Dant, J (1991) A fast, simple method for preparing flat semi-thin sections from epoxy embedded materials. J Electron Microsc Tech 18:209
Turner, D F; Marfurt, C F; Sattelberg, C (1989) Demonstration of physiological barrier between pulpal odontoblasts and its perturbation following routine restorative procedures: a horseradish peroxidase tracing study in the rat. J Dent Res 68:1262-8
Marfurt, C F; Kingsley, R E; Echtenkamp, S E (1989) Sensory and sympathetic innervation of the mammalian cornea. A retrograde tracing study. Invest Ophthalmol Vis Sci 30:461-72
Crutcher, K A; Marfurt, C F (1988) Nonregenerative axonal growth within the mature mammalian brain: ultrastructural identification of sympathohippocampal sprouts. J Neurosci 8:2289-302

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