Czech and Slovak Ophthalmology 50 Original article Clinical Manifestation of Experimental Autoimmune Uveitis Klímová Aneta https://orcid.org/0000-0002-3658-4429 Seidler Štangová Petra Svozílková Petra https://orcid.org/0000-0002-9221-0210 Kučera Tomáš Heissigerová Jarmila https://orcid.org/0000-0002-2614-4681 30 1 2016 1 3

Introduction: Autoimmune uveitis is a sight threatening disease which in many cases fails to respond to conventional immunosuppressive or biological therapy. The research in experimental models of autoimmune uveitis helps to find new therapeutical strategies. The aim of this study is to present the clinical and histological signs of experimental autoimmune uveitis (EAU) in mice. Methods: EAU was induced in C57BL/6 mice by subcutaneous application of IRBP (interphotoreceptor retinoid binding protein) in complete Freund’s adjuvant and intraperitoneal application of pertussis toxin. Clinical evaluation of uveitis was performed in vivo using special imaging system with otoscope. Histological evaluation of uveitis was performed at day 35 post induction of EAU on hematoxylin and eosin stained frozen sections. Clinical and histological grading was used to assess the inflammation intensity of EAU. Results: The intensity of inflammation is depicted on representative fundus images and histological images of retina at day 35 post induction. Conclusion: The model of EAU is robust and reproducible and allows us to study the immunopathological mechanisms of inflammation and its regulation. The inflammatory signs inour model are similar to findings of posterior uveitis of autoimmune etiology in humans, thus we may apply our experimental results in human medicine.

 experimental autoimmune uveitis autoimmunity mice References Agarwal R.K., Silver P.B., Caspi R.R.: Rodent Models of Experimental Autoimmune Uveitis. Autoimmunity: Methods and Protocols, Methods in Molecular Biology, vol. 900, Springer Science+Business Media New York; 2012, Chapter Sci, 41; 2000: 127–131. Avichezer D., Silver P. B., Chan C. C., Wiggert B. et al.: Identification of a new epitope of human IRBP that induces autoimmune uveroretinitis in mice of the H-2b haplotype. Invest Ophthalmol Vis Broderick C., Hoek R. M., Forrester J. V. et al.: Constitutive retinal CD200 expression regulates resident microglia and activation state of inflammatory cells during experimental autoimmune uveoretinitis: a model system for immunointervention: a review. Curr Eye Res, 11 (Suppl.): 33–40. Caspi R. R., Roberge F. G., Chan C. C.: A new model of autoimmune disease. Experimental autoimmune uveoretinitis induced in mice with two different retinal antigens. J Immunol, 140(5); 1988: 1490–1495. Caspi R. R.: Animal models of autoimmune and immune-mediated uveitis. Drug Discovery Today: Disease Models, Volume 3, Issue 1, 2006, 3–9. Caspi R. R., Silver P. B., Luger D. et al.: Mouse models of experimental autoimmune uveitis. Ophthalmic Res, 40; 2008: 169–74. Chan C. C., Caspi R. R., Ni M. et al.: Pathology of experimental autoimmune uveoretinitis in mice. J Autoimmun, 3; 1990: 247–55. Dick A. D., Cheng Y. F., Liversidge J. et al.: Immunomodulation of experimental autoimmune uveoretinitis: a model of tolerance induction with retinal antigens. Eye (Lond), 8 (Pt 1), 1994: 52–59. Durrani O. M., Meads C. A., Murray P. I.: Uveitis: a potencially blinding disease. Ophthalmologica, 218; 2004: 223–36. Forrester J. V., Worgul B. V., Merriam G. R., Jr.: Endotoxin-induced uveitis in the rat. Albrecht Von Graefes Arch Klin Exp Ophthalmol, 213; 1980: 221–33. Forrester J. V., Liversidge J., Dua H. S. et al. (1992): Experimental autoimmune Experimental Model of Autoimmune Uveitis. Folia Biologica (Praha), 2014; 60: 228–234. Hirose S., Singh V. K., Donoso L. A. et al.: An 18-mer peptide derived from the retinal S antigen induces uveitis and pinealitis in primates. Clin Exp Immunol, 77; 1989: 106–11. Jiang H.R., Lumsden L., Forrester J.V.: Macrophages and dendritic cells in IRBP-induced experimental autoimmune uveoretinitis in B10RIII mice. Invest Ophthalmol Vis Sci, 40 (13); 1999: 3177–85. Keino H., Kezuka T., Takeuchi M., et al.: Prevention of experimental autoimmune uveoretinitis by vasoactive intestinal peptide. Arch Ophthalmol. Aug, 2004; 122(8): 1179–84. Kim T.W., Jeong H.J., Lee H.J. et al.: Intraperitoneal Infusion of Mesenchymal Stem/Stromal Cells Prevents Experimental Autoimmune Uveitis in Mice. Mediators Inflamm, 2014: 624-640. Kitamei H., Kitaichi N., Yoshida K. et al.: Association of heat shock protein 70 induction and the amelioration of experimental autoimmune uveoretinitis in mice. Immunobiology, 2006; 212(1):11– 8. Klímová A., Seidler Štangová, J. Heissigerová et al.: Mycophenolate Mofetil and Cyclophosphamide Treatments Suppress Inflammation Intensity in an uveoretinitis. Am J Pathol, 161(5); 2002: 1669–77. Lalive dE-Z.: Experimental uveitis in the rat after subcutaneous injection of Freund‘s adjuvant. Histological changes in the uvea. Ophthalmologica, 155; 1968: 271–89. Paques M., Guyomard J. L., Simonutti M. et al.: Panretinal, High Resolution Color Photography of the Mouse Fundus. Invest. Ophthalmol Vis Sci, 48; 2007: 2769–2774. Suttorp-Schulten M. S., Rothova A.: The possible impact of uveitis in blindness: a literature survey. Br J Ophthalmol, 80; 1996: 844–848. Thurau S. R., Chan C. C., Nussenblatt R. B. et al.: Oral tolerance in a murine model of relapsing experimental autoimmune uveoretinitis (EAU): induction of protective tolerance in primed animals. Clin Exp Immunol, 109; 1997: 370–376. Wacker W. B., Kalsow C. M.: Autoimmune uveo-retinitis in the rat sensitized with retina photoreceptor cell antigen. Int Arch Allergy Appl Immunol, 45; 1973: 582–92. Xu H., Koch P., Chen M. et al.: A clinical grading system for retinal inflammation in the chronic model of experimental autoimmune uveoretinitis using digital fundus images. Exp Eye Res, 87; 2008: 319–326.