This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Lamellar corneal refractive surgery (procedures such as PRK, LASEK, LAS IK and CK that are commonly performed to correct myopia, hyperopia and astigmatism) leads to keratocyte apoptosis in the stroma adjacent to the epithelial surgical injury. This apoptosis, in turn, leads to activation of adjacent keratocytes, transformation and migration of fibroblasts and myofibroblasts, and alterations of the extracellular matrix.These events include an up-regulation of cytokine release and chemotaxis of inflammatory cells to the wound site. Although most patients heal without complications, some develop a state called 'dry eye' characterized by a dry ocular surface and loss of trophic factors that leads to epithelial breakdown and increased inflammation which can, in some cases lead to abnormal scarring and vision impairment. The different signals that lead to normal or abnormal healing of the cornea are poorly understood. Our hypothesis is that 'differences in macrophage or dendritic cell function may in part determine whether there is an adequate healing of the cornea or there is an impaired healing process after refractive surgery'. We will therefore focus our studies on the characterization of macrophages and dendritic cells (DC), both antigen presenting cells and the inflammatory mediators induced by refractive surgery, in models of normal or abnormal healing. The proposed studies use PRK in mouse cornea as the experimental model. The long-term goal of this research is to understand the mechanisms leading to abnormal healing of the cornea after surgery, and develop clinical studies to test whether modulation of the immune response can prevent or reverse abnormal healing.
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