Keratocyte regulation in corneal repair

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DESCRIPTION (From the Applicant's Abstract): The long-term objectives are to determine the molecular basis of phenotype regulation and define the contributions of the keratocyte, fibroblast and myofibroblast phenotypes to normal corneal biology as well as the response to stromal wounding. A model cell culture system allowing the investigator to reproduce keratocyte to fibroblast and fibroblast to myofibroblast transitions as well as reverse the myofibroblast to fibroblast transition will be utilized. The general hypothesis to be tested in this application is that the three corneal stromal cell phenotypes: keratocyte, fibroblast and myofibroblast are controlled by the interaction of three dominant factors; cell-matrix interactions; cell-cell interactions; and growth factors. The four specific aims will test the hypotheses that: (1) matrix generated signals are essential modulators of the fibroblast/myofibroblast phenotypes. (2) CTGF acts as a matrix signal to influence phenotype, migration and proliferation. (3) uPA and its interaction with transmembrane proteins modulates cellular function. (4) ZO-1 is involved in the fibroblast to myofibroblast transition.