The long-term goal of this project is to better understand the biological properties of corneal and conjunctival epithelial stem cells. Information about the location and properties of these stem cells is central to understanding the mechanisms involved in the maintenance and differentiation of these epithelia. The focus of this grant is to further define the stem and transient amplifying cell populations in corneal epithelium. In addition, in view of the intimate relationship between corneal and conjunctival epithelia, we will extend some of these investigations to include conjunctival epithelium. During this grant period we will use a combination of light and transmission electron microscopy, cell and organ culture, and tissue section autoradiography to study these problems using SENCAR mice and rabbits as experimental animals. We will: 1. further define the differences in the proliferative potential of limbal, peripheral and central corneal epithelia; 2. determine the rate and driving force for centripetal migration in normal corneal epithelium; 3. define the cell cycle phase durations in limbal, peripheral and central corneal epithelia; 4. determine whether during vitamin A deficiency the keratinized conjunctival epithelium is limbal-derived; and 5. study the location of """"""""label-retaining cells"""""""" in conjunctival epithelium. Information from these studies should lead to a better understanding of the roles of the limbal and corneal epithelia in growth control and differentiation. It should also lead to a better understanding of the interrelationship between conjunctival and corneal epithelia. This will ultimately increase our knowledge on diseases of the ocular surface epithelia such as persistent corneal epithelial defect and the various dry- eye conditions.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY006769-06
Application #
3263393
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1987-12-01
Project End
1996-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
6
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
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
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
Jensen, P J; Lavker, R M (1999) Urokinase is a positive regulator of epidermal proliferation in vivo. J Invest Dermatol 112:240-4

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