Functions of Bowman's Membrane and its Type V Collagen

鲍曼氏膜及其 V 型胶原蛋白的功能

• 批准号: 6415061
• 负责人: THOMAS Frank LINSENMAYER
• 金额: $ 15.85万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6415061
• 关键词: basal lamina; biological models; cell differentiation; cell growth regulation; cell membrane; cell migration; chickens; collagen; cornea; corneal epithelium; extracellular matrix; eye injury; eye laser surgery; eye prosthesis; growth factor; membrane activity; membrane permeability; protein binding; protein structure function; protein transport; wound healing

DESCRIPTION: (Applicant's Abstract) Bowman's membrane is a major component of the cornea that has been little studied - with virtually no information available as to whether this unique extracellular matrix has functional and regulatory properties. If it does have such properties, it will be important to elucidate these, since, (1) this layer is lost/ablated during certain types of injuries and laser corrective procedures, and (2) none of the synthetic corneal prosthesis that have been devised includes a Bowman's membrane equivalent which may be necessary to provide a long-term, functional prosthesis. In addition, most of the animal models in current use for corneal wounding studies (e.g., rabbits and rodents), may not be directly applicable to the human since the corneas of these species lack a Bowman's membrane. However, our previous studies on the chicken eye have shown that the cornea of this species has all of the major features of human cornea, including a Bowman's Membrane that is indistinguishable from that of the human. Thus we will use this species as an animal model for the human cornea. This application is based in part on our observation that a unique aspect of Bowman's membrane - which differentiates it from all other matrices we have examined - is the presence of type V Collagen in a form that exposes on the molecule potentially functional domains, such as ones that bind regulatory factors. We propose to examine whether Bowman's membrane, and its type V Collagen, may have unique properties that regulate certain aspects of corneal epithelial behavior (e.g., migration, proliferation and differentiation). To test this, the behavior of the corneal epithelium will be examined in vivo and in vitro on corneal surfaces in which excimer laser ablation has been used to selectively expose, as the matrix substratum for the epithelium, Bowman's Membrane or the epithelial basal lamina or the stroma proper.Other experiments will examine whether recombinant type V Collagen can substitute for Bowman's membrane, and, if so, whether the regulatory properties of the molecule involve its binding of specific growth factors. If Bowman's membrane and its type V Collagen do serve as a source of such factors, to reach the epithelium these must be able to pass across the corneal epithelial basal lamina, and this will also be tested. These experiments should provide clinically relevant information on the short and long term effects of this matrix on corneal wound healing and subsequent corneal maintenance following excimer laser corrective procedures, and wounding in general. They should also provide information as to whether, in a fabricated synthetic cornea, it will be advantageous - or even necessary - to include a subepithelial layer of type V Collagen to provide a Bowman's membrane equivalent.

描述：（申请人的摘要）鲍曼的膜是 几乎没有研究的角膜 - 几乎没有信息 可用于此独特的细胞外矩阵是否具有功能性和 监管特性。如果确实具有这样的特性，那么 阐明这些，因为（1）在某些类型的 伤害和激光矫正程序，（2）没有合成角膜 设计的假体包括鲍曼的膜量等效物 提供长期，功能性假体可能是必要的。此外， 当前用于角膜伤的研究中的大多数动物模型（例如 兔子和啮齿动物），可能不直接适用于人类 这些物种的角膜缺乏鲍曼的膜。但是，我们的先前 关于鸡眼的研究表明，该物种的角膜具有全部 人角膜的主要特征，包括鲍曼的膜 与人类没有区别。因此，我们将使用该物种作为 人角膜的动物模型。此应用程序部分基于我们 观察鲍曼膜的独特方面 - 区分它 从我们检查的所有其他矩阵中 - 存在V型胶原蛋白的存在 以暴露于分子潜在功能域的形式，例如 结合调节因素的人。我们建议检查鲍曼是否 膜及其型V胶原蛋白可能具有调节的独特特性 角膜上皮行为的某些方面（例如，迁移，增殖 和分化）。为了测试这一点，角膜上皮的行为将 在体内和体外检查在角膜表面上，在该表面上进行了激光 消融已被用于选择性暴露，作为矩阵底层 上皮，鲍曼的膜或上皮基底层或基质 其他实验将检查重组V型胶原蛋白是否可以 代替鲍曼的膜，如果是的，则是监管特性 该分子涉及特定生长因子的结合。如果鲍曼的 膜及其V型胶原蛋白确实是此类因素的来源，以达到 这些上皮必须能够穿过角膜上皮的基础 Lamina，这也将进行测试。这些实验应提供 有关此的短期和长期影响的临床相关信息 角膜伤口愈合和随后的角膜维护的基质 准分子激光矫正程序，通常受伤。他们也应该 提供有关是否在制造的合成角膜中的信息 有利的甚至是必要的 - 包括V型的下皮下层 胶原蛋白提供鲍曼的膜量。