The unique organization and structure of the corneal epithelium, stroma and endothelium are critical to the shape, transparency and protective functions of the cornea. Physical, chemical or infectious damage can result in repair tissues that have compromised structure, function poorly or have recurrent healing problems, often requiring corneal surgery or transplantation. Therefore, we wish to understand the basic mechanisms that regulate the migration, proliferation, and differentiation of these cells during normal development and during regeneration or repair. Specifically, we are focusing on the molecular regulation of these critical, active processes. Our previous work strongly implicates the small GTPase, Rho, and its downstream target kinase named ROCK in regulating corneal epithelial proliferation, cell-cell communication and corneal stromal activation.
The Specific Aims are directed at testing some very reasonable, yet crucial, hypotheses about the mechanism of involvement of Rho signaling in these processes. Specifically: 1) Rho/ROCK signaling directs corneal epithelial proliferation, through regulation of the cell cycle. 2) Rho/ROCK signaling regulates corneal epithelial cell-cell communication via connexin 43 gap junctions during the cell cycle progression and, in turn, has direct effects on gap junctional regulation of cell cycle progression. 3) Corneal stromal cell activation and inactivation is controlled by conjoint Rho/ROCK and Rho/mDial signaling. The first two aims will employ rabbit corneal epithelial cells and the third aim employs rabbit corneal stromal cells, in culture. The evaluation of these hypotheses will advance our knowledge of the molecular signaling mechanisms that sustain corneal homeostasis and wound healing. That knowledge may lead to the development of methods for modulating cellular activation, cell-cell communication, differentiation and proliferation, which are critical to new interventions to improve corneal wound healing.
| 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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