The long range goal of this project is to understand the mechanisms of corneal development, maintenance and regeneration. The results will be applicable to the better management of corneal healing and prevention of blindness. The research strategy is to evaluate the functional significance of changes in the expression of specific proteins which are regulated during these processes. We are focusing on a Rho (Ras homology)-associated in serine/threonine kinase (ROCK-I) whose expression is significantly increased in the corneal epithelial cells after they migrate from the limbal to corneal surface. Rho belongs to the Ras family of small GTPases, which control a variety of cellular processes involving cell proliferation, actin filament reorganization and phospholipid metabolism. ROCK-I is one of the downstream components of Rho signaling pathways. Our immediate goals are to understand the mechanisms of ROCK-I involvement in the signaling cascade in the corneal epithelium. To achieve these goals, our specific aims are to test the following hypotheses: 1) ROCK-I is involved in corneal epithelial migration, differentiation and proliferation and that these functions of ROCK-I require its intracellular translocation. This will be tested in vitro in cultured rabbit corneal epithelial cells. 2) Phosphorylation by a cAMP-dependent protein kinase (PKA) is involved in controlling the enzyme activity and nuclear translocation of ROCK-1. 3) diacylglycerol (DAG), a second messenger formed by receptor triggered hydrolysis of phosphotidyl inositol, 4, 5 biphosphate (PIP2), promotes the intracellular translocation of ROCK-I. These studies will lead to the identification of RhoA and ROCK-I signaling elements which may be specific targets for new drugs, useful for modulating corneal epithelial repair.
| Lathrop, Kira L; Gupta, Divya; Kagemann, Larry et al. (2012) Optical coherence tomography as a rapid, accurate, noncontact method of visualizing the palisades of Vogt. Invest Ophthalmol Vis Sci 53:1381-7 |
| Gupta, Divya; Du, Yiqin; Piluek, Jordan et al. (2012) Ethyl pyruvate ameliorates endotoxin-induced corneal inflammation. Invest Ophthalmol Vis Sci 53:6589-99 |
| Chen, Jian; Wong-Chong, Julie; SundarRaj, Nirmala (2011) FGF-2- and TGF-?1-induced downregulation of lumican and keratocan in activated corneal keratocytes by JNK signaling pathway. Invest Ophthalmol Vis Sci 52:8957-64 |
| Harvey, Stephen A K; Guerriero, Emily; Charukamnoetkanok, Nahthai et al. (2010) Responses of cultured human keratocytes and myofibroblasts to ethyl pyruvate: a microarray analysis of gene expression. Invest Ophthalmol Vis Sci 51:2917-27 |
| Chen, Jian; Guerriero, Emily; Sado, Yoshikazu et al. (2009) Rho-mediated regulation of TGF-beta1- and FGF-2-induced activation of corneal stromal keratocytes. Invest Ophthalmol Vis Sci 50:3662-70 |
| Shen, Xiang; Koga, Takahisa; Park, Bum-Chan et al. (2008) Rho GTPase and cAMP/protein kinase A signaling mediates myocilin-induced alterations in cultured human trabecular meshwork cells. J Biol Chem 283:603-12 |
| Chen, Jian; Guerriero, Emily; Lathrop, Kira et al. (2008) Rho/ROCK signaling in regulation of corneal epithelial cell cycle progression. Invest Ophthalmol Vis Sci 49:175-83 |
| Guerriero, Emily; Chen, Jian; Sado, Yoshikazu et al. (2007) Loss of alpha3(IV) collagen expression associated with corneal keratocyte activation. Invest Ophthalmol Vis Sci 48:627-35 |
| Du, Yiqin; Sundarraj, Nirmala; Funderburgh, Martha L et al. (2007) Secretion and organization of a cornea-like tissue in vitro by stem cells from human corneal stroma. Invest Ophthalmol Vis Sci 48:5038-45 |
| Chen, Jianxin; Li, Hongxia; SundarRaj, Nirmala et al. (2007) Alpha-smooth muscle actin expression enhances cell traction force. Cell Motil Cytoskeleton 64:248-57 |
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