Protein Mediated Protection from Microbial Keratitis

蛋白质介导的微生物性角膜炎保护

• 批准号: 6736542
• 负责人: Mitchell C. Sanders
• 金额: $ 10万
• 依托单位: ECI BIOTECH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6736542
• 关键词: Pseudomonas aeruginosa; bacteria infection mechanism; bacterial cytopathogenic effect; chimeric proteins; contact lens; corneal epithelium; crystallins; drug design /synthesis /production; keratitis; metalloendopeptidases; protease inhibitor; protein structure function; tissue /cell culture

DESCRIPTION (provided by applicant): Microbial keratitis is a serious eye infection that can lead to permanent vision loss through corneal scarring or perforation. Pseudomonas aeruginosa is one of the most frequent ocular isolates and has been shown to be associated with 75% of contact lens mediated infectious keratitis. Contact lens wearers are more prone to microbial keratitis and the development of new therapies is an important field of research. The current practice is to treat the infection with antibiotics, but the recent emergence of resistant bacterial strains has heightened the need for alternative treatments. Although the exact sequence of events leading to microbial keratitis has not been fully elucidated, the role of the host and microbial proteases in keratitis has been well documented. This application proposes the use of a novel "Protector protein" mediated technology as an alternative regimen for combating keratitis. "Protector proteins" are novel molecules that have two distinct classes of activities. The first obvious activity is protein stabilization via refolding while the second less obvious but equally impressive group of Protector proteins, belong to the class of protease inhibitors. Our hypothesis is that ECI characterized "Protector proteins"; alphaA-Crystallin, gammaD-Crystallin and the chimeric protein, pepstatin/leupeptin/alphaA-Crystallin will inhibit the proteolytic enzymes secreted by the host and the pathogen, thus serving as a good therapeutic agent against the management of microbial keratitis. The specific aims designed for phase I of SBIR grant, are based on this premise and will provide us with significant in vitro biochemical analysis leading way to more telling in vivo animal model studies. We envisage that attachment of these "Protector proteins" onto extended wear soft contact lenses would significantly reduce the incidence of microbial keratitis associated with contact lens wearers and could attract significant portion of this market. In summary, this application proposes the use of a novel "Protector protein" mediated technology as an alternative regimen for combating keratitis.

描述（由申请人提供）：细菌性角膜炎是一种严重的眼部感染，可通过角膜瘢痕或穿孔导致永久性视力丧失。铜绿假单胞菌是最常见的眼部分离株之一，已被证明与75%的隐形眼镜介导的感染性角膜炎有关。隐形眼镜佩戴者更容易患微生物角膜炎，开发新的治疗方法是一个重要的研究领域。目前的做法是用抗生素治疗感染，但最近出现的耐药菌株增加了对替代治疗的需求。虽然导致微生物性角膜炎的事件的确切顺序尚未完全阐明，但宿主和微生物蛋白酶在角膜炎中的作用已被充分记录。本应用建议使用一种新的“保护蛋白”介导技术作为对抗角膜炎的替代方案。“保护蛋白”是一种新型分子，具有两种不同的活性。第一个明显的活性是通过再折叠来稳定蛋白质，而第二个不太明显但同样令人印象深刻的保护器蛋白组属于蛋白酶抑制剂。