EXPERIMENTAL FUNGAL INFECTIONS OF THE EYE

眼部实验性真菌感染

基本信息

批准号：
2882869
负责人：
Denis M O'Day
金额：
$ 34.04万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1979
资助国家：
美国
起止时间：
1979-04-01 至 2000-12-31
项目状态：
已结题

项目摘要

The overall aim of this research is to develop more effective treatment for fungal keratitis. To accomplish this objective, there is a need to study the separate but related infectious and inflammatory process that occur simultaneously and to develop pharmacological treatment that combines effective antifungal and antiinflammatory measures. The PI will examine the role of ocular cyclooxygenases in the inflammatory response to fungal infection in the cornea and anterior uvea. The regulation and cellular distribution of rabbit ocular cyclooxygenase 1 and 2, which he have recently cloned, will be established during thevarious stages of fungal keratitis. Also, the integrity of the bolls aqueous barrier, recruitment of inflammatory cells, and changes inthe aqueous prostaglandin levels will be establihsed. These experiments will allow the PI to better understand the molecular basis of fungal keratitis. Changes in the expression of Candida CYP51, which is required for fungal cell wall production and is a target of azole compounds, will be determine and used as a marker of the metabolic state of viable fungi during antifungal treatment. By using this method along with quantitative isolate recovery the PI will be able to determine both the metabolic state of fungi and the number of azole antifungal compounds. Finanly, he will determine the efficacy of azole antifungal agents alone and in combination with antiinflammatory agents using our model of fungal keratitis. This will be accomplished by methods that we have established to assess the ocular inflammatory response and metabolic state of the invading fungi.

这项研究的总体目的是开发更有效的治疗用于真菌性角膜炎。为了实现这一目标，有必要研究单独但相关的传染和炎症过程同时发生，并开发出药理治疗结合了有效的抗真菌和抗炎措施。 PI将检查眼部环氧酶在对角膜和前感染真菌感染的炎症反应乌维亚。兔眼的调节和细胞分布他最近克隆的环氧合酶1和2将是在真菌角膜炎的变化阶段建立。另外，孔屏障的完整性，炎症的募集细胞，前列腺素水平的变化将是建立。这些实验将使PI更好地理解真菌性角膜炎的分子基础。念珠菌CYP51表达的变化，这是必需的真菌细胞壁生产，是偶氮化合物的靶标确定并用作可行真菌的代谢状态的标记在抗真菌治疗期间。通过使用此方法以及定量分离株恢复PI将能够确定真菌的代谢状态和硫代抗真菌的数量化合物。他将单独确定偶氮抗真菌剂的功效并结合我们的模型与抗炎药结合真菌角膜炎。这将通过我们拥有的方法来完成建立以评估眼部炎症反应和代谢入侵真菌的状态。