The anterior surface of the eye is covered by several physically contiguous but histologically distinct epithelia overlying the cornea, limbus and conjunctiva. As self-renewing tissues, these epithelia are governed by stem cells which play a crucial role in tissue homeostasis, regeneration and tumorigenesis. Our earlier work has helped to establish that corneal epithelial stem cells are preferentially located in the limbal zone. This finding has improved our understanding of corneal epithelial diseases and their treatment. Much less is known, however, about the location of conjunctival epithelial stem cells. Our recent data suggests that conjunctival epithelial stem cells are enriched in the fornical zone, and that conjunctival goblet cells are able to divide and thus may play a role in maintaining and repairing the conjunctival epithelium. The long-term goal of this project is to understand the biological properties of corneal and conjunctival epithelial stem cells. Towards this end we will: (i) localize the conjunctival epithelial stem cells, by in vitro and in vivo experiments comparing the proliferative properties of bulbar, fornical and palpebral epithelial cells; (ii) determine the role of the goblet cell in conjunctival homeostasis, by light and transmission electron microscopy, cell culture, autoradiography and a athymic mouse/epithelial cyst system; and (iii) identify proteins elaborated by fibroblasts underlying~the corneal, limbal and conjunctival epithelia using the random primer-PCR technique. Data obtained from these studies, should help us understand the role of stem cells in corneal and conjunctival epithelia in growth control and differentiation. These studies should ultimately lead to a better understanding and therapy of ocular surface disorders including persistent corneal epithelial defect and various dry-eye conditions.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY006769-10
Application #
2391698
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1987-12-01
Project End
2000-03-31
Budget Start
1997-04-01
Budget End
1998-03-31
Support Year
10
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Dermatology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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
Park, Jong Kook; Peng, Han; Katsnelson, Julia et al. (2016) MicroRNAs-103/107 coordinately regulate macropinocytosis and autophagy. J Cell Biol 215:667-685
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
Peng, Han; Hamanaka, Robert B; Katsnelson, Julia et al. (2012) MicroRNA-31 targets FIH-1 to positively regulate corneal epithelial glycogen metabolism. FASEB J 26:3140-7
Sun, Lijie; Ryan, David G; Zhou, Mingyuan et al. (2006) EEDA: a protein associated with an early stage of stratified epithelial differentiation. J Cell Physiol 206:103-11
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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