REGULATION OF SCLERAL GROWTH AND REMODELLING

巩膜生长和重塑的调节

• 批准号: 2331653
• 负责人: Jody A Summers
• 金额: $ 15.37万
• 依托单位: UNIVERSITY OF NORTH DAKOTA
• 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 2000-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2331653
• 关键词: age difference; autoradiography; cell growth regulation; chickens; collagen; collagenase; drug adverse effect; extracellular matrix proteins; glycoprotein biosynthesis; human tissue; immunoelectron microscopy; in situ hybridization; injection /infusion; morphology; myopia; northern blottings; organ culture; pathologic process; polymerase chain reaction; proteoglycan; radiotracer; sclera; tissue inhibitor of metalloproteinases; transmission electron microscopy

The sclera, a connective tissue consisting of proteoglycans and collagen, provides the structural integrity that defines the shape and focal length of the eye. Therefore, alterations in the synthesis, degradation and net accumulation of these extracellular matrix components are likely to lead to significant changes in eye shape and severely affect vision. High myopia is a common condition characterized by excessive lengthening of the eye, primarily due to elongation of the vitreous chamber. Generally, myopia develops before puberty, and then stabilizes. If axial elongation fails to stabilize, an individual has an increased risk of retinal detachment, glaucoma, and blindness. This proposal examines the hypothesis that myopia is a connective tissue disorder in which the scleral extracellular matrix components are inappropriately remodeled. The objective of this proposal is to characterize the biochemical events which lead to scleral elongation and to identify regulatory mechanisms that govern these events. The well established model of myopia in chicks (form deprivation myopia) will be used to determine whether: 1) proteoglycan accumulation within the chick sclera is directly responsible for normal and myopic scleral growth, 2) changes in the fibrous sclera of form-deprived chick eyes parallel changes observed in myopic mammalian sclera 3) regional extracellular matrix turnover is mediated by the regulation of the 72 kDa gelatinase (MMP-2) and its associated inhibitors (TIMP-1 and TIMP-2) in the normal and form-deprived sclera, and 4) changes in the visual environment trigger the differential expression of genes within the eye which regulate scleral growth. Additionally, we propose to characterize the extracellular matrix of the human sclera from donors ranging in age from fetal - 90 years, in order to identify structural and biochemical differences which would predispose children to the development of myopia. Together, this information will serve as a basis for understanding the mechanisms by which myopia develops in chicks as well as in humans. Ultimately, this information may lead to the development of an anti-myopia therapy in children which would slow the progression of myopia by altering scleral metabolism and growth.

巩膜是一种结缔组织，由蛋白聚糖和胶原蛋白组成， 提供定义形状和焦距的结构完整性 眼睛。因此，合成，降解和净的改变 这些细胞外基质组件的积累可能会导致 眼睛形状的重大变化并严重影响视力。高的 近视是一种常见疾病，其特征是过度延长 眼睛，主要是由于玻璃体腔的伸长。一般来说， 近视在青春期之前发展，然后稳定。如果轴向伸长 无法稳定，一个人的视网膜风险增加 分离，青光眼和失明。该提案检查了 近视是一种结缔组织障碍的假设 巩膜外基质组件的重塑不当。 该建议的目的是表征生化事件 这导致巩膜伸长并确定调节机制 管理这些事件。小鸡中近视的良好模型 （形式剥夺近视）将用于确定是否：1） 小鸡巩膜内的蛋白聚糖积聚是直接负责的 对于正常和近视巩膜的生长，2）纤维巩膜的变化 在近视哺乳动物中观察到的形式不足的小鸡的平行变化 巩膜3）区域细胞外基质周转率由 调节72 kDa明胶酶（MMP-2）及其相关抑制剂 （TIMP-1和TIMP-2）在正常和形式的巩膜中，4） 视觉环境的变化触发了差异表达 眼睛内的基因调节巩膜生长。另外，我们 提议表征人类巩膜的细胞外基质 胎儿年龄的捐助者 - 90岁，以确定 结构性和生化差异会使儿童容易 近视的发展。在一起，这些信息将作为 理解近视发展机制的基础 小鸡和人类。最终，这些信息可能导致 开发儿童的抗果皮疗法，这会减慢 通过改变巩膜代谢和生长来进展。