Regulation of tissue repair and scar formation by the stromal niche

Project Description/ Abstract Corneal scarring is a public health problem and a very common indication for corneal transplantation. Disorganized deposition of extracellular matrix or scarring occurs after different pathological processes including corneal infections, congenital diseases and trauma. The long term goal of this proposal is to address the innovative concept that reestablishment of a unique environment or stromal niche with its unique mechanical and chemical cues is critical after injury to ameliorate scarring. Understanding the mechanisms that direct reestablishment of stromal function after injury is a potential target for therapuetic interventions. Our preliminary results support these concepts. The specific aims are to: (1) elucidate the regulation of collagen V reexpression in the reestablishment of corneal stroma function; (2) determine the role of this unique microenvironment in regulating keratocyte-fibroblast- myofibroblast differentiation; and (3) determine the roles of collagens V, in regulating latent TGF-β activation and therefore modulating matrix deposition and scarring. This work will provide critical information for the development of future medical or surgical therapies for patients with corneal scarring and will open the door for therapeutic manipulation of the corneal stroma.