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P.S. Kulkarni, N.S. Bora, J. Sohn, H.J. Kaplan; The Complete Inhibition of Experimental Autoimmune Uveitis (eaau) in Lewis Rats by Cycloxygenase-2 Inhibitor, cs236 . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4594.
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Purpose: Inflammation, in general, causes the release of a variety of inflammatory mediators that in turn induce cyclooxygenase (COX) 2, nitric oxide synthase (iNOS) and 5-lipoxygense (LP) synthesis producing large amounts of proinflammatory prostaglandins (PG), NO and leukotriene (LT) B4. . Therefore, inhibition of these enzymes may abrogate intraocular inflammation-i.e. EAAU. Methods: Lewis rats were immunized by the footpad injection of bovine melanin associated antigen (100 mg, MAA). These animals were divided into three groups. The first group of rats received subcutaneous injection of COX 2 inhibitor CS 236 at different intervals, respectively. The second and third of animals received subcutaneous aminoguanidine (AG), iNOS inhibitor, and nordihydroguaeretic acid (NDGA), 5-LP inhibitor, respectively. Control animals received vehicle. Rat eyes were examined by daily slit-lamp examination from day 7to30 post injection for EAAU. Results: Clinical and histopathological examinations of control rat eyes showed severe EAAU with onset on the 10th day and a duration of 10 days. In contrast, iNOS inhibitor (AG) and 5-LP inhibitor (NDGA) partially attenuated EAAU. Interestingly, CS 236, a potent COX 2 inhibitor, completely abrogated EAAU when the animals were treated from the day 0 to 20 after MAA injection. Furthermore, CS 236 treatment after the onset of EAAU (day 14-20) significantly inhibited development of EAAU and shortened the duration of disease. Conclusions: In the present study, AG and NDGA partially attenuated EAAU. However, CS236, a potent COX 2 inhibitor, completely inhibited EAAU in male Lewis rats; most likely by inhibiting the initial phase and onset of the disease. This is very interesting because the Lewis rat EAAU model is similar to human anterior uveitis.
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