The anterior cornea is richly invested with sensory neuronal fibers that contain the 11 residue neuropeptide substance P (SP). Within the eye this peptide has been shown to have a variety of effects, but its function within the cornea has not been clearly elucidated. Preliminary studies demonstrate that: 1) SP stimulates DNA synthesis in corneal epithelial cells; 2) Depletion or impairment of SP release from neurons markedly impaired corneal epithelial wound healing; 3) Topical SP application to a neuropeptide depleted cornea accelerates the wound healing process in an animal model; 4) SP stimulates the migration of corneal epithelial cells; 5) SP stimulates the attachment of corneal epithelial cells; 6) SP promoted the healing of neurotrophic ulcers in a canine clinical trial; and 7) SP promoted the healing of corneal ulcers in two human patients. Studies proposed in this proposal will: 1) determine a formulation of SP and SP analogs for addition to the eye; 2) determine the stability of SP and SP analogs under different time and temperature conditions; and 3) determine SP and SP analog dosage for the treatment of eye diseases.
