MOLECULAR STUDIES OF THE THIEL-BEHNKE CORNEAL DYSTROPHY

Thiel-Behnke 角膜营养不良的分子研究

• 批准号: 7103846
• 负责人: Richard W Yee
• 金额: $ 1.17万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7103846
• 关键词: MOLECULAR; STUDIES; THIEL; BEHNKE; CORNEAL

EXCEED THE SPACEPROVIDED. The overall goal of our research is to determine and understand the genes and the molecular mechanisms that will lead to a broad overview and understanding of corneal transparency in inherited corneal disorders of the anterior stroma and Bowman's membrane complex. Once the disease-causing gene(s) for ThieI-Behnke corneal dystrophy (CDB2) are cloned and characterized, this research will shed light on the associated mechanisms of wound healing and scarring, the most common cause for corneal transplantation. Genetic defects in the cornea in humans can result in serious loss of visual function with accompanying symptoms of severe pain, tearing and photophobia. Given the relatively large number of affected individuals, it is imperative that the inheritable corneal diseases become the focus of intense study and their treatments become a high priority, j3ig-h3, the causative gene for Reis-B0cklers' corneal dystrophy (CDB1), and the yet to be identified causative gene for ThieI-Behnke (CDB2) may play a crucial role in corneal transparency via its structural role in the extracellular matrix of the cornea. The similar clinical phenotypes of the two diseases may suggest that CDB2 also plays a vital role in wound healing and scarring of the Bowman's membrane complex. Engineering transgenic mice that express mutant proteins will enhance our understanding of developmental mechanisms and functions of the cornea at the molecular level. This will be accomplished by elucidating the promoter and enhancer elements of the disease causing gene through the expression of mutant forms and assessment on the phenotypic impact in the cornea. As the causative gene(s) are characterized through these transgenic models, it should be possible to design specialized therapies based on knowledge of the underlying biochemical, structural and metabolic defect. Eventually, this information should also be of use in determining the genetic cause of these diseases in other patients and will contribute, ultimately, to diagnosis, counseling, prevention and/or treatment. PERFORMANCESITE( ========================================Section End===========================================

超出所提供的空间。 我们研究的总体目标是确定和了解基因和分子机制，这将导致对前基质和鲍曼膜复合体遗传性角膜疾病中角膜透明度的广泛概述和理解。一旦ThieI-Behnke角膜营养不良（CDB 2）的致病基因被克隆和鉴定，这项研究将揭示伤口愈合和瘢痕形成的相关机制，这是角膜移植最常见的原因。 人类角膜的遗传缺陷会导致严重的视觉功能丧失，伴随着剧烈疼痛、流泪和恐惧症的症状。鉴于受影响的个体数量相对较大，遗传性角膜疾病必须成为深入研究的焦点，并且其治疗成为高度优先事项，j3 ig-h3，Reis-Bocklers角膜营养不良（CDB 1）的致病基因，以及尚未鉴定的ThieI-Behnke（CDB 2）致病基因可能通过其在角膜细胞外基质中的结构作用在角膜透明度中起关键作用。这两种疾病相似的临床表型可能表明CDB 2在创伤愈合和Bowman膜复合体的瘢痕形成中也起着至关重要的作用。 表达突变蛋白的工程转基因小鼠将增强我们在分子水平上对角膜发育机制和功能的理解。这将通过阐明致病基因的启动子和增强子元件，通过突变形式的表达和评估角膜中的表型影响来实现。由于致病基因通过这些转基因模型表征，因此应该可以基于对潜在的生化、结构和代谢缺陷的了解来设计专门的疗法。最终，这些信息也应该用于确定其他患者这些疾病的遗传原因，并最终有助于诊断，咨询，预防和/或治疗。网站（==