Regulation of Scleral Growth and Remodeling in Myopia

近视眼巩膜生长和重塑的调节

• 批准号: 8077258
• 负责人: Jody A Summers
• 金额: $ 31.54万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-01-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8077258
• 关键词: Adult; Affect; Animals; Biomechanics; Callithrix; Callithrix jacchus jacchus; Cellular biology; Choroid; Collagen Fibril; Connective Tissue; Data; Development; Disease; Environment; Extracellular Matrix; Eye; Financial compensation; Funding; Gene Expression; Growth; Human; Lead; Length; Liquid substance; Measures; Mediating; Metabolism; Molecular; Myopia; Permeability; Population; Property; Proteoglycan; Proteomics; Recovery; Regulation; Sclera; Shapes; Testing; Tissues; Vascular Permeabilities; Visual; Vitreous Chamber; Work; base; deprivation; design; insight; lens; novel; prevent; research study; response

DESCRIPTION (provided by applicant): Myopia is the most common of all ocular problems, affecting 25 percent of the US adult population. The most common structural abnormality associated with myopia is excessive lengthening of the posterior segment of the ocular globe (axial myopia). While it is clear that changes in the shape of the sclera produce myopia, the basis for this shape change is largely unknown. The sclera is a connective tissue, consisting of interwoven collagen fibrils in close association with proteoglycans that provides the structural framework that defines the shape and therefore the axial length of the eye. Past work by our lab and others has clearly demonstrated that the sclera is not a static container of the eye, but rather is a dynamic tissue, capable of altering extracellular matrix composition and its biomechanical properties in response to changes in the visual environment to regulate ocular size and refraction. The mechanism by which this visually-guided scleral remodeling is regulated is largely unknown. Preliminary data is presented in this proposal that implicates the choroid in the regulation of scleral metabolism. We hypothesize that changes in choroidal vascular permeability are responsible for the release of soluble factors that act on the sclera to regulate scleral proteoglycan synthesis and the rate of ocular elongation during visually guided ocular growth. Experiments outlined in the current application combine whole animal, cellular and molecular approaches to determine whether: 1) Changes in choroidal permeability correlate with the rate of scleral proteoglycan synthesis and rate of ocular elongation in chicks during visually guided ocular growth, 2) changes in scleral proteoglycan synthesis that occur during the development of form deprivation myopia (FDM), recovery from FDM, and during compensation for myopic and hyperopic defocus are regulated by changes in the composition of suprachoroidal fluid, and 3) ocular growth changes associated with the development of FDM, recovery from FDM and during compensation for myopic and hyperopic defocus are mediated by changes in choroidal gene expression. Results obtained from these studies will provide new information on choroidal function and cell biology, and provide insights into a novel mechanism of ocular growth regulation. Ultimately, this information may be applied to strategies to reverse or prevent the scleral extracellular matrix changes associated with myopia development.

描述（由申请人提供）：近视是所有眼部问题中最常见的，影响了美国成年人口的25％。与近视相关的最常见的结构异常是眼球后段过度延长（轴向近视）。虽然很明显，巩膜形状的变化产生了近视，但这种形状变化的基础在很大程度上是未知的。巩膜是一种结缔组织，由与蛋白聚糖密切相关的交织胶原蛋白原纤维组成，该蛋白聚糖提供了定义形状的结构框架，因此是眼睛的轴向长度。我们的实验室和其他人的过去工作清楚地表明，巩膜不是眼睛的静态容器，而是一种动态组织，能够改变细胞外基质组成及其生物力学特性，以响应视觉环境的变化以调节角度和折射。这种视觉引导的巩膜重塑受到调节的机制在很大程度上尚不清楚。该提案中介绍了初步数据，该数据暗示了脉络膜的巩膜代谢。我们假设脉络膜血管通透性的变化是导致作用于巩膜作用的可溶性因子以调节巩膜蛋白聚糖合成的可溶性因子，并且在视觉引导的眼部生长过程中释放了巩膜蛋白聚糖的合成和眼部伸长率的速率。 Experiments outlined in the current application combine whole animal, cellular and molecular approaches to determine whether: 1) Changes in choroidal permeability correlate with the rate of scleral proteoglycan synthesis and rate of ocular elongation in chicks during visually guided ocular growth, 2) changes in scleral proteoglycan synthesis that occur during the development of form deprivation myopia (FDM), recovery from FDM, and在补偿近视和触角散焦的过程中，由甲状腺液体组成的变化和3）与FDM发展，FDM回收以及近视和近视伸缩的补偿时的眼部生长变化是由脉络膜基因表达的变化所介导的。从这些研究中获得的结果将提供有关脉络膜功能和细胞生物学的新信息，并提供有关眼部生长调节机制的新颖机制。最终，这些信息可以应用于逆转或防止巩膜外基质变化与近视开发相关的策略。