Ocular surface is a continuous structure of cornea and conjunctiva where abnormal epithelial cell movement can lead to blinding conditions, such as when conjunctival cells move into the cornea. Some unique features of ocular surface homeostasis suggest that cell movement may be regulated by stem cells and their niches. Thus, the goal of the proposal is to identify stem cells and stem cell niches at the origins of homeostatic cell movements, and to investigate their role as a regulator of cell movement.
Five specific aims will guide the project: First and second aims are to determine precise location and distribution of epithelial stem cells of the cornea and the conjunctiva, respectively. This information is expected to facilitate molecular characterization of stem cells. Clinically, this knowledge is likely to benefit stem cell transplantation for reconstruction of damaged ocular surface.
Third aim will investigate the presence of stem cell niches and their movement in the limbus and the conjunctiva for the first time.
Fourth aim i s to determine the ability of stem cells and niche cells to regulate cell movement and maintain homeostasis, which may lead to a novel method of manipulating ocular surface cell movement.
Fifth aim i s to examine the effect of aging on ocular surface homeostasis in a quantitative manner. This knowledge is relevant in management of ocular surface damage in aging populations, and also in use of aged ocular surface components for grafting. To achieve these aims, two determinants of homeostasis - cell movement and cell division - will be analyzed. Cell movement will be tracked in a living mouse, taking advantage of the in vivo microscopy technique developed in this laboratory. Rates of mitosis will be determined in ocular surface whole-mount preparations. Results from this investigation will establish basic parameters of ocular surface homeostasis, such as location and density of stem cells, rates of mitosis, and rates of cell movement, which will help to characterize ocular surface damage for possible treatment of the condition. It is hoped that these findings will eventually lead to better management of diseases and injuries of the ocular surface, as well as successful engineering of artificial ocular surface.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-AED (01))
Program Officer
Shen, Grace L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Columbia University (N.Y.)
Schools of Medicine
New York
United States
Zip Code
Silverman, Erika; Zhao, Jin; Merriam, John C et al. (2017) Intracellular Position of Centrioles and the Direction of Homeostatic Epithelial Cell Movements in the Mouse Cornea. J Histochem Cytochem 65:83-91
Zhao, Jin; Mo, Victoria; Nagasaki, Takayuki (2009) Distribution of label-retaining cells in the limbal epithelium of a mouse eye. J Histochem Cytochem 57:177-85
Zhang, W; Zhao, J; Chen, L et al. (2008) Abnormal epithelial homeostasis in the cornea of mice with a destrin deletion. Mol Vis 14:1929-39