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: 6524801
• 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/6524801
• 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）鲍曼氏膜（Bowman’s membrane）是膜的主要组分。 几乎没有人研究过角膜， 关于这种独特的细胞外基质是否具有功能性和 监管属性。如果它确实具有这样的特性， 阐明这些，因为，（1）该层在某些类型的 损伤和激光矫正手术，和（2）没有合成角膜 已经设计出的假体包括鲍曼膜等效物， 可能是提供长期功能性假体所必需的。此外，本发明还提供了一种方法， 目前用于角膜损伤研究的大多数动物模型（例如， 兔子和啮齿动物），可能不直接适用于人类，因为 这些物种的角膜缺乏鲍曼氏膜。然而，我们以前的 对鸡眼的研究表明，这种物种的角膜具有所有 人类角膜的主要特征，包括鲍曼膜， 与人类的相似。因此，我们将使用这个物种作为一个 人类角膜的动物模型。该应用程序部分基于我们的 鲍曼氏膜的一个独特的方面-这使它与其他膜不同， 从我们检查过的所有其他基质中-是V型胶原蛋白的存在 以暴露分子上潜在功能结构域的形式，例如 那些结合调节因素的。我们建议检查鲍曼的 膜及其V型胶原蛋白可能具有独特的特性， 角膜上皮行为的某些方面（例如，迁移、扩散 差异化）。为了验证这一点，角膜上皮的行为将 在体内和体外对角膜表面进行检查， 烧蚀已被用于选择性地暴露，作为用于 上皮、Bowman膜或上皮基底层或间质 其他实验将检查重组V型胶原蛋白是否可以 鲍曼膜的替代品，如果是这样的话， 该分子的功能涉及其与特定生长因子的结合。如果鲍曼 膜及其V型胶原蛋白确实是这些因子的来源， 这些上皮必须能够穿过角膜上皮基底 这也将被测试。这些实验应该提供 关于短期和长期影响的临床相关信息 基质对角膜伤口愈合和随后的角膜维护的影响 准分子激光矫正手术和一般的创伤。他们也应该 提供关于在制造的合成角膜中， 有利的-或甚至必要的-包括V型上皮下层 胶原蛋白提供鲍曼氏膜等效物。