Corneal Epithelial Stem Cells

角膜上皮干细胞

• 批准号: 7880383
• 负责人: ROBERT M LAVKER
• 金额: $ 30.26万
• 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 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7880383
• 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; self-renewal; 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).

描述：眼睛的前表面充当外部环境的障碍，并保护精致的基础结构免受损伤。这种保护是通过阐述角膜，边缘和结膜上皮的阐述，以及巨腺腺，这有助于形成撕裂膜。作为自我更新的组织，这些上皮受到干细胞的控制，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理中起着至关重要的作用。在过去的二十年中，我的工作有助于鉴定梅博米亚腺的角膜，结膜和导管上皮部分中的干细胞。我们最近的数据表明，在小鼠膜膜层基础上皮细胞的子集中，Epiregulin是调节细胞增殖和伤口愈合的有效生长因子。由于角膜上皮干细胞位于缘层层基础上皮中，因此我们假设上环蛋白在调节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否对称或不对称地分裂，以及它们在多大程度上可以改变其分裂方式； （ii）进一步识别和表征干细胞偏爱的分子，通过转录富含干细胞富含前表面的上皮； （iii）研究了在角膜上皮生长调节中表达的上环蛋白的作用。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的生长和分化中的作用。这些研究应为更好地理解与边缘细胞缺乏缘长的某些问题的病因构成基础（例如，持续的角膜上皮分解以及肿瘤转化，从而产生眼部上皮肿瘤）。