The long term goal of this project is to better understand the biological properties of corneal epithelial stem cells. The focus of this grant is to test the hypothesis that the limbal epithelium has a greater proliferative potential than the corneal epithelium. If this is the case, it would provide strong experimental evidence that corneal epithelial stem cells reside primarily in the limbus and may migrate toward the center of the cornea. During this granting period we will use a combination of light and transmission electron microscopy and tissue section autoradiography to study this problem using SENCAR mice, rabbits and monkeys as experimental animals. We will: 1. study the role of limbal epithelial cells during corneal wound healing; 2. study the role of limbal epithelial cells in tumorigenesis; 3. study the replacement of limbal and corneal epithelial cells by conjunctiva-derived epithelial cells; 4. study the """"""""label-retaining cells"""""""" in corneal and limbal epithelia, and study the movement of such tagged cells. Information from these studies should allow us to decide whether limbal epithelium has a greater proliferative potential than corneal epithelium. It should also lead to a better understanding of the possible roles of the limbal and corneal epithelia in growth control, differentiation and carcinogenesis. This will ultimately increase our knowledge on the structure and function of corneal and limbal epithelia in man.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Visual Sciences A Study Section (VISA)
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University of Pennsylvania
Schools of Medicine
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Kaplan, Nihal; Ventrella, Rosa; Peng, Han et al. (2018) EphA2/Ephrin-A1 Mediate Corneal Epithelial Cell Compartmentalization via ADAM10 Regulation of EGFR Signaling. Invest Ophthalmol Vis Sci 59:393-406
Dong, Ying; Peng, Han; Lavker, Robert M (2018) Emerging Therapeutic Strategies for Limbal Stem Cell Deficiency. J Ophthalmol 2018:7894647
Peng, Han; Park, Jong Kook; Lavker, Robert M (2017) Autophagy and Macropinocytosis: Keeping an Eye on the Corneal/Limbal Epithelia. Invest Ophthalmol Vis Sci 58:416-423
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Peng, Han; Park, Jong Kook; Katsnelson, Julia et al. (2015) microRNA-103/107 Family Regulates Multiple Epithelial Stem Cell Characteristics. Stem Cells 33:1642-56
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Zhou, Mingyuan; Leiberman, Joshua; Xu, Jing et al. (2006) A hierarchy of proliferative cells exists in mouse lens epithelium: implications for lens maintenance. Invest Ophthalmol Vis Sci 47:2997-3003
Jensen, P J; Lavker, R M (1999) Urokinase is a positive regulator of epidermal proliferation in vivo. J Invest Dermatol 112:240-4
Williams, D L; Risse, B; Kim, S et al. (1999) Plasminogen activator inhibitor type 2 in human corneal epithelium. Invest Ophthalmol Vis Sci 40:1669-75

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