Cornea is a transparent avascular tissue which consists of three cell layers, the epithelium, stroma and endothelium. The unique organization and structure of these cell layers are critical to the transparency of the cornea. Our current research interests include the mechanisms of the homeostasis of the corneal epithelium, a self-renewing tissue, and the activation of corneal stromal cells during wound healing. Recently, we have recognized that Rho (a Ras related small GTPase) signaling pathway(s) plays a critical role in the corneal epithelia homeostasis. An increased expression of a down stream target of RhoA, Rho-associated serine/threonine kinase (ROCK-I) is one of the phenotypic changes associated with the corneal epithelial cells as they migrate centripetally over the corneal surface from the limbus. Studies are in progress to characterize the mechanisms of involvement of Rho signaling pathway(s) in corneal epithelial cell cycle, cell-cell communication via gap junctions, and cell-cell adhesion through adherence junctions.

Rho signaling also plays a role in the assembly of actin filaments which are dynamic structures in the cells, associated with a variety of cellular processes including cell migration and cellular contraction. During corneal stromal wound healing the stromal keratocytes are activated to fibroblasts and myofibroblasts. Our studies have indicated that Rho signaling via its effectors ROCK and Dia1 (a homolog of Drosophila diaphanous) are involved in this activation process. We are currently investigating the mechanisms of involvement of ROCK and mDia in the assembly of the actin filament network in the corneal fibroblasts (migratory cells) and myofibroblasts (contractile cells).

The structure and function of extracellular matrices (ECMs) are critical in the development and maintenance of corneal transparency. Structural alterations ECM resulting in the loss of transparency can be a consequence of injury to the corneal stroma or corneal dystrophies. Keratoconus is one of the more prevalent corneal dystrophies, which causes progressive thinning of the central part of the cornea and in advanced cases development of corneal scarring and opacity. It has been one of the most common reasons for corneal transplantation. We found that type XII collagen distribution is altered in corneas of the patients with keratoconus. Our previous analyses had indicated that the long variant form of type XII collagen may contribute to the unique structure and function of corneal epithelial and stromal ECMs. Currently we are testing the hypothesis that type XII collagen gene is mutated in some keratoconus patients and the mutated forms of type XII collagen are responsible for the assembly of altered ECM which is prone to break-down by specific proteases.