Corneal Epithelial Stem Cells

角膜上皮干细胞

• 批准号: 7235608
• 负责人: ROBERT M LAVKER
• 金额: $ 55.94万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-12-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7235608
• 关键词: Adopted; Anterior; Basal Cell; Biologic Characteristic; Biological; Cell Lineage; Cell Proliferation Regulation; Cells; Conjunctival Epithelium; Cornea; Data; Differentiation and Growth; Disease; Ductal; Ductal Epithelium; Environment; Epiregulin; Epithelial; Epithelial Attachment; Epithelial Cells; Epithelium; Etiology; Eye; Eyelid structure; Film; Foundations; Frozen Sections; Goals; Grant; Growth; Growth Factor; Homeostasis; Injury; Mus; Natural regeneration; Nature; Neoplastic Cell Transformation; Pathogenesis; Play; Property; Regulation; Role; Series; Site; Stem cells; Structure; Surface; Techniques; Tissue Transplantation; Tissues; Work; Wound Healing; cDNA Arrays; conjunctiva; corneal epithelial stem cells; corneal epithelium; gene therapy; laser capture microdissection; limbal; meibomian gland; ocular surface; research study; trafficking; tumor

DESCRIPTION: 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).

产品说明：眼睛的前表面作为外部环境的屏障，保护脆弱的底层结构免受伤害。这种保护是通过角膜、角膜缘和结膜上皮以及睑板腺的发育提供的，睑板腺有助于泪膜的形成。作为自我更新的组织，这些上皮细胞由干细胞控制，干细胞在组织稳态、再生、组织移植、基因治疗以及几种前表面上皮疾病的发病机制中起关键作用。在过去的二十年里，我的工作有助于识别角膜，结膜和睑板腺导管上皮部分内的干细胞。我们最近的数据表明，epiregulin，一个有效的生长因子参与调节细胞增殖和伤口愈合，优先表达在小鼠角膜缘基底上皮细胞的一个子集。由于角膜上皮干细胞位于角膜缘基底上皮中，我们假设表皮调节蛋白在调节角膜缘上皮干细胞的增殖性质中起关键作用。该项目的长期目标是了解眼表上皮干细胞的生物学特性，重点是角膜和结膜的上皮干细胞。为此，我们将：（i）确定眼前表面上皮中的干细胞是对称分裂还是不对称分裂，以及它们能在多大程度上改变其分裂模式;（ii）通过对前表面的干细胞富集的上皮进行转录谱分析来进一步鉴定和表征干细胞偏好的分子;和（iii）研究在角膜缘上皮基底细胞亚群中表达的表皮调节蛋白在角膜上皮生长调节中的作用。从这些研究中获得的数据应有助于我们了解干细胞在控制角膜和结膜上皮细胞的生长和分化中的作用。这些研究应该为更好地理解与角膜缘干细胞缺乏相关的某些问题的病因奠定基础（例如，持续的角膜上皮破裂，以及产生眼上皮肿瘤的肿瘤转化）。