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Lichun Zhong, Laxman S Desai, Ocular Department, Toxikon Corporation; Comparison of Endotoxin-Induced Uveitis Model and Experimental Autoimmune Uveitis Model in Lewis Rats for Drug Screening. Invest. Ophthalmol. Vis. Sci. 2014;55(13):94.
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The study is to compare Endotoxin-Induced Uveitis (EIU) and Experimental Autoimmune Uveitis (EAU) Models in Lewis Rats in order to choose appropriate models for anti-inflammatory drug screening.
The EIU model was induced by endotoxin named lipopolysaccharides (LPS) through footpad injection on Day 0 in 49 Lewis rats included five groups: negative control of saline (Saline); positive control of dexamethasone + low dose lipopolysaccharides (Dex + LLPS); positive control of dexamethasone + high dose lipopolysaccharides (Dex+ HLPS); low dose lipopolysaccharides (LLPS); and high dose lipopolysaccharides (HLPS). The EAU model induced by a subcutaneous injection of peptide R16 of bovine interphotoreceptor Retinoid Binding Protein (IRBP) on Day 1 in 30 Lewis rats included three groups: negative control of saline (Saline); positive control of dexamethasone + IRBP (Dex + IRBP) and IRBP. Animals were sacrificed on Day 2 or 3 (EIU), and on 21 (EAU).
In EIU, inflammation of eyes in Dex. + LLPS, Dex + HLPS, LLPS and HLPS groups was scored significantly higher than the Saline group (P < 0.05). The inflammation scores in LLPS and HLPS groups were significantly more severe than scores in Dex + LLPS, Dex + HLPS groups (P < 0.05). The inflammation presented a peak at 48 hours. The inflammatory cells in eye tissues in Dex + LLPS, Dex + HLPS, LLPS and HLPS groups were significantly increased when compared to the Saline group (P < 0.05). Concentration levels of ICAM-1, IL-6, MCP-1 and TNF-alpha in retina increased in various extents in Dex + LLPS, Dex + HLPS, LLPS and HLPS groups. In EAU, Inflammation of eyes in IRBP group was scored significantly higher than the Saline group (P < 0.05) and the peak at Day 14. The inflammation scores were significant different when compared to that in the Saline or Dex + IRBP groups (p<0.05). Inflammatory and degenerative changes were detected in the retina tissue in IRBP group.
The EIU and EAU models were successfully induced and the peak of inflammation was at 48 hours (EIU) or Day 14 (EAU). Dex effectively inhabited the inflammation in both models. Both of EIU and EAU models may provide a stable, effective and reliable method for anti-inflammatory drug screening.
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