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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY001621-21
Application #
2668364
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1979-04-01
Project End
2000-02-29
Budget Start
1998-03-01
Budget End
1999-02-28
Support Year
21
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Braun, B R; Head, W S; Wang, M X et al. (2000) Identification and characterization of TUP1-regulated genes in Candida albicans. Genetics 156:31-44
Wang, M X; Shen, D J; Liu, J C et al. (2000) Recurrent fungal keratitis and endophthalmitis. Cornea 19:558-60
O'Day, D M; Head, W S (2000) Advances in the management of keratomycosis and Acanthamoeba keratitis. Cornea 19:681-7
O'Day, D M; Head, W S; Csank, C et al. (2000) Differences in virulence between two Candida albicans strains in experimental keratitis. Invest Ophthalmol Vis Sci 41:1116-21
O'Day, D M; Head, W S; Robinson, R D et al. (1999) Contact lens-induced infection--a new model of Candida albicans keratitis. Invest Ophthalmol Vis Sci 40:1607-11
Chang, M S; Tsai, J C; Yang, R et al. (1997) Induction of rabbit cyclooxygenase 2 in the anterior uvea following glaucoma filtration surgery. Curr Eye Res 16:1147-51
Lamps, C A; Oeltmann, T N; Collins Jr, M J et al. (1995) Development of a chitin assay for the quantification of fungus. Curr Eye Res 14:637-41
Klippenstein, K; O'Day, D M; Robinson, R D et al. (1993) The qualitative evaluation of the pharmacokinetics of subconjunctivally injected antifungal agents in rabbits. Cornea 12:512-6
O'Day, D M; Head, W S; Robinson, R D et al. (1992) The evaluation of therapeutic responses in experimental keratomycosis. Curr Eye Res 11:35-44
O'Day, D M; Head, W S; Robinson, R D et al. (1992) Ocular pharmacokinetics of saperconazole in rabbits. A potential agent against keratomycoses. Arch Ophthalmol 110:550-4

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