zed from abstract) Pseudomonas aeruginosa is an opportunistic pathogen that causes corneal necrosis, ulceration and scarring. The keratitis produced is among the most rapidly spreading and destructive bacterial diseases of the cornea known, often resulting in blindness. The investigators experimental model uses C57Bl/6 mice that are susceptible to bacterial keratitis, since they fail to repair corneal damage and restore corneal clarity following infections with P.aeroginosa. Parental immunization with dead bacteria results in a rapid restoration of corneal clarity within a few days. The investigator hypothesizes that different responses to infection between the susceptible mice and immunized mice may be due in part to their ability to regulate corneal tissue remodeling and repair, and to restore corneal clarity after infection. Tissues remodeling and repair, or damage, that accompanies infection and inflammation are highly regulated cellular processes in which the degradation of the extracellular matrix (ECM) plays a critical role. ECM degradation is largely controlled by a superfamily of Zn dependent proteolytic enzymes called metalloproteinases (MMPs) and their naturally occurring tissue inhibitors of metalloproteinases (TIMPs). Therefore, the investigator proposes to characterize different TIMPs in normal corneal tissue and after P.aeruginosa infection in susceptible and immunized mice. He will use biochemical, immunohistochemical and in situ mRNA hybridization techniques to study the spatial and temporal gene expression of TIMPs in normal and infected corneas, and correlate these data with the progression of corneal repair or damage. This model provides a versatile microbiological, immunological, and molecular genetic tool for the development of potential therapy to protect against corneal damage.
| Berk, Richard S; Dong, Zhong; Alousi, Sarah et al. (2004) Murine ocular heparanase expression before and during infection with Pseudomonas aeruginosa. Invest Ophthalmol Vis Sci 45:1182-7 |
| Dong, Z; Katar, M; Linebaugh, B E et al. (2001) Expression of cathepsins B, D and L in mouse corneas infected with Pseudomonas aeruginosa. Eur J Biochem 268:6408-16 |
| Berk, R S; Katar, M; Dong, Z et al. (2001) Plasminogen Activators and Inhibitors in the Corneas of Mice Infected with Pseudomonas aeruginosa. Invest Ophthalmol Vis Sci 42:1561-7 |
| Dong, Z; Katar, M; Alousi, S et al. (2001) Expression of membrane-type matrix metalloproteinases 4, 5, and 6 in mouse corneas infected with P. aeruginosa. Invest Ophthalmol Vis Sci 42:3223-7 |
| Dong, Z; Ghabrial, M; Katar, M et al. (2000) Membrane-type matrix metalloproteinases in mice intracorneally infected with Pseudomonas aeruginosa. Invest Ophthalmol Vis Sci 41:4189-94 |
