The objectives of the current study are: 1) to analyze critically at both the LM and EM levels the structure, origin, and nature of the corneal innervation and 2) to determine the brainstem projections and synaptic connections of corneal afferent neurons. In the first series of experiments, horseradish peroxidase (HRP) will be injected into either the trigeminal, superior cervical, or ciliary ganglion of rats and monkeys. The enzyme will be taken up by the neuronal cell bodies and transported anterogradely to the peripheral nerve endings in the cornea. Each population of labeled neural elements will then be analyzed critically to determine its origin, distribution, ultrastructure, and mode of termination within the cornea. In addition, detailed electron microscopic studies of human corneal innervation will be performed on corneas obtained from fresh autopsy material and from patients whose corneas have been excised for corneal transplant. In a second set of experiments, the significance of the vesicles found in many corneal nerve terminals will be investigated. Experiments will be performed in animal models to determine if the vesicles (containing most likely trophic or neurotransmitter substances) can be released from the corneal nerve terminals by antidromic stimulation of the ophthalmic nerve or mechanical stimulation of the corneal surface. Substance P (SP)-containing fibers in human and animal corneas will be examined critically at both the LM and EM level with respect to their structure, distribution, and mode of termination. In animal models, it will be determined if these fibers release SP from their terminals following antidromic stimulation of the ophthalmic nerve or mechanical stimulation of the corneal surface. Finally, the brainstem sites of termination of corneal afferent neurons will be determined experimentally at the LM and EM levels by the method of transganglionic transport of HRP. The distribution, ultrastructure, and synaptic relationships of the fibers will be analyzed to determine the CNS substrates subserving corneal sensation and corneal reflexes. The results of the present study should increase significantly our understanding of the anatomy of the corneal innervation, the role of the corneal innervation in corneal physiology, and the peripheral and central neural mechanisms of corneal sensation.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY005717-02
Application #
3261101
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1984-07-01
Project End
1987-12-31
Budget Start
1985-07-01
Budget End
1987-12-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
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
Marfurt, C F; Echtenkamp, S F (1988) Central projections and trigeminal ganglion location of corneal afferent neurons in the monkey, Macaca fascicularis. J Comp Neurol 272:370-82

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