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.

巩膜是一种由蛋白聚糖和胶原蛋白组成的结缔组织， 提供定义形状和焦距的结构完整性 眼睛的。因此，合成、降解和净值的改变 这些细胞外基质成分的积累可能会导致 使眼睛形状发生显着变化并严重影响视力。高的 近视是一种常见病症，其特征是视力过度延长 眼睛，主要是由于玻璃体腔的伸长。一般来说， 近视在青春期前形成，然后稳定。如果轴向伸长 未能稳定，个体患视网膜病变的风险增加 脱离、青光眼和失明。该提案审查了 假设近视是一种结缔组织疾病，其中 巩膜细胞外基质成分被不当重塑。 该提案的目的是描述生化事件的特征 导致巩膜伸长并确定调节机制 管理这些事件。完善的雏鸡近视模型 （形觉剥夺性近视）将用于确定是否：1) 鸡巩膜内蛋白多糖的积累是直接原因 对于正常和近视巩膜生长，2) 纤维巩膜的变化 形状剥夺的雏鸡眼睛的变化与近视哺乳动物中观察到的相似 巩膜 3) 区域细胞外基质周转由 72 kDa 明胶酶 (MMP-2) 及其相关抑制剂的调节 （TIMP-1 和 TIMP-2）在正常和形态剥夺的巩膜中，4） 视觉环境的变化引发差异表达 眼睛内调节巩膜生长的基因。此外，我们 提议表征人类巩膜的细胞外基质 捐献者的年龄从胎儿到90岁不等，以便识别 结构和生化差异可能会导致儿童 到近视的发展。这些信息共同将作为 为了解近视发展机制奠定基础 小鸡和人类一样。最终，这些信息可能会导致 开发一种儿童抗近视疗法，可以减缓 通过改变巩膜代谢和生长来加剧近视。