Recent work in our laboratory has shown that the response of mice to challenge with Pseudomonas aeruginosa varies with the age of the animal. Inoculation of the bacteria under the unopened eyelid of young (5 and 10 day old) Swiss and DBA/2 mice with no prior corneal trauma, resulted in bacteremia and death in 80-100 percent of the animals. Endophthalmitic occurred in 30 percent of the bacteremic mice surviving to age 15 days. In 15-16 day old mice whose eyelids were opened, bacterial challenge onto wounded corneas only, produced eye shrinkage (phthisis bulbi) in 50 percent of the mice. Results of similar studies in 21 day old mice were follows: 37 percent became microphathalmic and cataractous: 32 percent recovered spontaneously and 29 percent exhibited phthisis bulbi. Adult mice (4-6 weeks old) of these strains, on the other hand, respond to corneal wounding and infection with pseudomonas by spontaneously resolving the infection in 4 weeks. Aged mice respond to corneal trauma and bacterial infection in a manner similar to the 15-16 day old mice. Therefore, these studies suggested that infection with pseudomonas provides an appropriate experimental model for examining the change with age of resistance to bacterial infection. This project encompasses the following general areas of study: (1) an extensive survey and characterization of the age-related changes in natural resistance of the eye to challenge with pseudomonas; (2) a comprehensive ultrastructural analysis of the ocular tissues at various ages before and after a bacterial challenge to the eye. These studies employing histopathological, immunocytochemical and histochemical techniques will follow the morphological responses of infected animals' eyes at the light and electron microscopic levels; (3) attempts to identify the cellular, tissue and humoral factors which may control age-related susceptibility of the eye to pseudomonas infection. Although this model is restricted to the eye, the results may have significance on a systemic basis. The use of the eye allows one to study a specific restricted organ system, thereby simplifying experimental design and data interpretation.
| McClellan, Sharon A; Ekanayaka, Sandamali A; Li, Cui et al. (2015) Thrombomodulin Protects Against Bacterial Keratitis, Is Anti-Inflammatory, but Not Angiogenic. Invest Ophthalmol Vis Sci 56:8091-100 |
| McClellan, Sharon; Jiang, Xiaoyu; Barrett, Ronald et al. (2015) High-mobility group box 1: a novel target for treatment of Pseudomonas aeruginosa keratitis. J Immunol 194:1776-87 |
| Jiang, Xiaoyu; McClellan, Sharon A; Barrett, Ronald et al. (2014) HGF signaling impacts severity of Pseudomonas aeruginosa keratitis. Invest Ophthalmol Vis Sci 55:2180-90 |
| Li, Cui; McClellan, Sharon A; Barrett, Ronald et al. (2014) Interleukin 17 regulates Mer tyrosine kinase-positive cells in Pseudomonas aeruginosa keratitis. Invest Ophthalmol Vis Sci 55:6886-900 |
| Hazlett, Linda D; Jiang, Xiaoyu; McClellan, Sharon A (2014) IL-10 function, regulation, and in bacterial keratitis. J Ocul Pharmacol Ther 30:373-80 |
| Foldenauer, Megan E B; McClellan, Sharon A; Berger, Elizabeth A et al. (2013) Mammalian target of rapamycin regulates IL-10 and resistance to Pseudomonas aeruginosa corneal infection. J Immunol 190:5649-58 |
| Berger, Elizabeth A; McClellan, Sharon A; Vistisen, Kerry S et al. (2013) HIF-1? is essential for effective PMN bacterial killing, antimicrobial peptide production and apoptosis in Pseudomonas aeruginosa keratitis. PLoS Pathog 9:e1003457 |
| Berger, Elizabeth A; Vistisen, Kerry S; Barrett, Ronald P et al. (2012) Effects of VIP on corneal reconstitution and homeostasis following Pseudomonas aeruginosa induced keratitis. Invest Ophthalmol Vis Sci 53:7432-9 |
| Jiang, Xiaoyu; McClellan, Sharon A; Barrett, Ronald P et al. (2012) The role of VIP in cornea. Invest Ophthalmol Vis Sci 53:7560-6 |
| Foldenauer, Megan E B; McClellan, Sharon A; Barrett, Ronald P et al. (2012) Substance P affects growth factors in Pseudomonas aeruginosa-infected mouse cornea. Cornea 31:1176-88 |
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