Abstract
Purpose :
Purpose: Uveitis describes the inflammation of the uveal tissues of the eye. Posterior uveitis, the inflammation of the choroid, can affect the retina and optic nerve and result in blindness. Lipopolysaccharide (LPS) is routinely used to induce a phenotype of infectious uveitis in rabbits. However, descriptions of the LPS-induced uveitis models differ in the literature. The purpose of this study is to characterize the LPS-induced model for infectious uveitis in pigmented Brown Norway rats using LPS derived from Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, and explore the effects of Peptidoglycan (PG) from Staphylococcus aureus.
Methods :
Methods: 30 Brown Norway rats were divided into five groups (n=6). Saline, LPS derived from E. coli, S. typhimurium, P. aeruginosa, or PG from S. aureus were delivered by single bilateral intravitreal injection. Slit-lamp ophthalmic exams were performed to monitor pathology such as vitreal haze and retinal edema, evaluated using the SPOTS system. Fundus imaging and IOP were performed at Baseline, Day 0, 2, 7, 14, and 21. Euthanasia was performed on Day 2, 7 and 14 or 21 (n=2/timepoint).
Results :
Results: Each of the test articles being explored had similar but distinct patterns of pathology. The PG group had a lower SPOTS score (mild phenotype) of 2 on Day 2 and decreased to 0 by Day 14. The LPS from the Pseudomonas species presented a moderate phenotype score of 3 on Day 2 and trailed off to 0 by Day 14. The E. coli presented a moderate to severe phenotype with an average score of 3.5 on Day 2 and a comparatively longer duration out to Day 21. S. typhimurium was the most severe phenotype with a median score of 3.5 on Day 2, 3.75 on Day 7, and decreasing to 0 by Day 21. There were significant differences between groups (P < 0.0001). There was no significant change in IOP for any of the groups at any time point.
Conclusions :
Conclusion: There is a distinct phenotype profile for each of the different cell wall components used in this exploratory study. Each induction article can be characterized with mild to severe symptoms over short to long duration. This enables tailoring of the model to better explore drug development. The LPS derived from S. typhimurium would be the most useful for drug development as it had the longest duration paired with high SPOTS scores.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.