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O. Delgado, S. Louie, M. Crowley, B. Jaffee, S.-M. Liao; Characterization of Anterior Segment Inflammation in a Rabbit Model of Endotoxin-Induced Uveitis (EIU). Invest. Ophthalmol. Vis. Sci. 2010;51(13):4832.
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To characterize and investigate the mechanism of anterior uveitis that occurs in a rabbit model of EIU by measuring inflammatory cell infiltration into the aqueous humor as a response to different parameters such as age, dose and time of LPS.
EIU was induced in male Dutch Belted rabbits by an ear intravenous injection of LPS in 0.5ml/kg PBS. Rabbits were euthanized at multiple time points. Ocular tissues such as aqueous humor, iris and retina-posterior cup were collected. To measure the number of inflammatory cells in the anterior chamber, the aqueous humor was aspirated using a 25G needle-syringe and a cytospin slide was prepared and stained using a Geimsa stain. In addition the iris was fixed in 4% paraformaldehyde and used for whole mount immuno-staining of neutrophils (RPN3/57). Ocular tissues were processed and prepared for Myeloperoxidase activity and cytokines/chemokines profiling to further characterize the ocular inflammation.
Following LPS exposure, various inflammatory markers (IL-6, IL-8 and MCP-1) were up-regulated in the aqueous humor and iris in a time dependent manner. A time and dose dependent infiltration of inflammatory cells into the aqueous humor and iris, not in posterior tissue, was also observed with a peak at 16 hours. This anterior inflammation appeared to be more prominent in twelve-week old rabbits in a dose dependent manner. To further characterize this model, several reference compounds were administered systemically, topically and locally via intravitreal (ivt) injection. Topical and systemic administration of the anti-inflammatory glucocorticoid, Dexamethasone significantly inhibited the LPS-induced neutrophil infiltration in the aqueous humor. Lastly, blocking one of the signal transduction pathways downstream of TLR4, the TNFα pathway, by anti-TNFα antibody (Enbrel) inhibited the anterior leukocyte accumulation even when delivered in the posterior segment of the eye by intravitreal injection.
Endotoxin induced uveitis is a useful model for studying inflammatory processes within the eye. Based on our study we found that a single systemic dose of LPS induces an anterior inflammation in Dutch Belted rabbits that can be significantly altered by age, dose and time of LPS. This anterior inflammation can be considerably inhibited by anti-inflammatory agents delivered locally or systemically.
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