MOLECULAR STUDIES OF THE THIEL-BEHNKE CORNEAL DYSTROPHY

Thiel-Behnke 角膜营养不良的分子研究

• 批准号: 7123576
• 负责人: Richard W Yee
• 金额: $ 22.03万
• 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/7123576
• 关键词: clinical research; cornea disorder; family genetics; gene expression; gene mutation; genetic regulatory element; human subject; microarray technology; molecular pathology; nucleic acid sequence; patient oriented research; polymerase chain reaction

DESCRIPTION (provided by applicant): 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 and wound healing in inherited corneal disorders of the anterior stroma and Bowman's membrane complex. Once the disease-causing gene(s) for Thiel-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 loss of vision necessitating in 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. Beta-ig-h3, the causative gene for Reis-Bucklers' 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 the CDB2 gene also plays a vital role in wound healing and scarring of the Bowman's membrane complex. Long term goals will include engineering transgenic animals 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 more accurate diagnosis, effective genetic counseling, and better regimens for prevention and/or treatment.

描述（由申请人提供）：我们研究的总体目标是确定和了解基因和分子机制，这将导致对角膜透明和伤口愈合在遗传性角膜前基质和鲍曼膜复合体疾病中的广泛概述和理解。一旦Thiel-Behnke角膜营养不良（CDB2）的致病基因被克隆和表征，这项研究将揭示伤口愈合和瘢痕形成的相关机制，这是角膜移植中导致视力丧失的最常见原因。