The anterior surface of the eye functions as a barrier to the external environment and protects the delicate underlying structures from injury. This protection is provided through the elaboration of the corneal, limbal and conjunctival epithelia, as well as the meibomian gland, which contributes to the formation of the tear film. As self-renewing tissues, these epithelia are governed by stem cells, which play a crucial role in tissue homeostasis, regeneration, tissue transplantation, gene therapy, and in the pathogenesis of several anterior surface epithelial diseases. My work during the past two decades has contributed to the identification of stem cells within the corneal, conjunctival and ductal epithelial portion of the meibomian gland. Our recent data indicates that epiregulin, a potent growth factor involved in the regulation of cell proliferation and wound healing, is preferentially expressed in a subset of mouse limbal basal epithelial cells. Since corneal epithelial stem cells are located in the limbal basal epithelium, we hypothesize that epiregulin plays a key role in regulating the proliferative nature of the limbal epithelial stem cells. The long-term goal of this project is to understand the biological properties of the stem cells of the ocular surface epithelium, with a focus on the epithelial stem cells of the cornea and conjunctiva. Towards this end we will: (i) determine whether the stem cells in the ocular anterior surface epithelium divide symmetrically or asymmetrically, and to what extent can they change their mode of division;(ii) further identify and characterize stem cell-preferred molecules by transcriptional profiling the stem cell-enriched epithelia of the anterior surface;and (iii) study the role(s) of epiregulin, which is expressed in a subset of limbal epithelial basal cells, in corneal epithelial growth regulation. Data obtained from these studies should help us to understand the role of stem cells in controlling growth and differentiation of the corneal and conjunctival epithelia. These studies should form the foundation for a better understanding of the etiology of certain problems associated with limbal stem cell deficiency (e.g., persistent corneal epithelial breakdown, as well as neoplastic transformations giving rise ocular epithelial tumors).

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY006769-23
Application #
7844834
Study Section
Anterior Eye Disease Study Section (AED)
Program Officer
Shen, Grace L
Project Start
1987-12-01
Project End
2012-04-30
Budget Start
2010-06-01
Budget End
2012-04-30
Support Year
23
Fiscal Year
2010
Total Cost
$591,527
Indirect Cost
Name
Northwestern University at Chicago
Department
Dermatology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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
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
Lavker, R M; Risse, B; Brown, H et al. (1998) Localization of plasminogen activator inhibitor type 2 (PAI-2) in hair and nail: implications for terminal differentiation. J Invest Dermatol 110:917-22
Risse, B C; Brown, H; Lavker, R M et al. (1998) Differentiating cells of murine stratified squamous epithelia constitutively express plasminogen activator inhibitor type 2 (PAI-2). Histochem Cell Biol 110:559-69
Rodeck, U; Jost, M; Kari, C et al. (1997) EGF-R dependent regulation of keratinocyte survival. J Cell Sci 110 ( Pt 2):113-21

Showing the most recent 10 out of 12 publications