Corneal Wound Healing Project Overview Corneal scarring is a major cause of decreased visual quality and vision loss worldwide. Causes of corneal scarring include almost any disruption to normal corneal structure and function, whether from infection, laser refractive surgery, corneal transplantation, ocular trauma (chemical or physical) or corneal dystrophies. There is no suitable means of controlling corneal scaring despite more than 25 years trying to characterize cytokine signaling during wound healing. Our ultimate goal is to understand mechanisms of corneal wound healing and to design effective therapies to treat or prevent corneal scarring. Our current research works to accomplish this by investigating a relative newcomer in the field of corneal pharmacologics: PPARγ ligands. PPARγ is a nuclear receptor/transcription factor, whose ligands are beginning to emerge as central elements in attenuation of inflammation and fibrosis in other body tissues. However, though highly promising, the role and mechanisms of action of PPARγ ligands as natural modulators of fibrosis in the cornea remain unexplored. Current clinical approaches to reduce corneal fibrosis are only partially effective and carry significant side effects, while PPARγ ligands are already clinically available as “insulin sensitizers” for diabetes. Therefore, the translational potential of our work is very high. Ongoing studies in the lab use both in vitro (cell culture) and in vivo (using a cat animal model of PRK-induced corneal wound healing) approaches to define the relative effectiveness and mechanisms of action of PPARγ ligands in the unique environment of corneal wounds. Our experiments are shedding light on the possibility that we could pharmacologically control different aspects of corneal wound healing by acting on different intracellular pathways within corneal keratocytes, epithelial and immune cells. Our in vitro experiments are designed to identify the intracellular signaling pathways activated by PPARγ ligands, whose effectiveness we are characterizing in parallel in vivo experiments. The uniqueness of our approach is that we can not only define biological and molecular aspects of corneal fibrosis, but also measure their optical consequences in vivo. Ultimately, what we are looking for is a treatment for fibrosis that preserves and restores the cornea’s structure, function and optical properties. We hope that this work will provide significant, meaningful new information that will have a major impact on the treatment of many types of corneal scarring in humans.