SUBSTANCE P FOR CORNEAL WOUND HEALING

DESCRIPTION (Adapted from the Investigator's Abstract): 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. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 306 --PROJECT NUMBER......2 R44 GM51147-02A1 INVESTIGATOR NAME/ADDRESS FY 97 SMALL, ENOCH W IRG/INTRAMURAL UNIT..ZRG3 QUANTUM NORTHWEST AWARD AMOUNT......... $331,891 9723 W SUNSET HIGHWAY SPOKANE, WA 99224 PERFORMING ORGANIZATION: QUANTUM NORTHWEST TITLE BIG BANG--FAST ALTERNATIVE TO STOPPED FLOW ABSTRACT: Our goal is to produce a commercial instrument which combines the laser- induced photolysis of photolabile caged compounds and acoustic detection to obtain very fast kinetic information on biological molecules. In Phase I we built a prototype pulsed-laser photoacoustic instrument and showed that it could be used to measure the rates associated with the binding of protons to polypeptides. We now propose instrumental and software improvements that will dramatically extend the time range over which we can make measurements, as well as the quality of information that we can obtain. Using the improved instrumentation, we will perform a survey of the kinetics of release for commercially available caged compounds, extending from the nitrophenylethyl(NPE-) caged proton we used in our Phase I studies, to the numerous faster releasing caged compounds currently available. We will also continue and extend our polypeptide studies, adding control experiments and obtaining corroborating evidence of molecular relaxations using other kinetic approaches. The product of our work will provide researchers with a new tool to measure molecular relaxations by their kinetics, enthalpic changes, and volumetric changes, in a very important submillisecond time range, without the requirements of an intrinsic molecular chromophore.