Clinical and Functional Evaluation of Ocular Inflammatory Disease Using the Model of Experimental Autoimmune Uveitis

  • Jun ChenEmail author
  • Rachel R. Caspi
Part of the Methods in Molecular Biology book series (MIMB, volume 1899)


Non-infections uveitis in humans is an autoimmune disease of the retina and uvea that can be blinding if untreated. Its laboratory equivalent is experimental autoimmune uveitis (EAU) induced in susceptible rodents by immunization with retinal antigens and described elsewhere in this series (Agarwal et al., Methods Mol Biol, 900:443–469, 2012). Evaluation and quantitation of the disease is usually performed by fundus examination and/or histopathology, which provide limited information on structural and no information on functional changes as disease progresses. Here, we describe methods for systematic evaluation of disease using noninvasive clinical assessments by fundus examination and photography, optical coherence tomography, and functional evaluation by electroretinography, which are then compared to histopathology. Using these methodologies, we demonstrate that clinical variants of disease can be accurately evaluated both clinically and functionally, facilitating longitudinal follow-up and providing information that cannot be obtained by fundoscopy and histology alone. These methodologies can be useful to obtain additional information and to evaluate effects of therapeutic modalities under investigation.

Key words

Uveitis EAU Autoimmunity T cells Tolerance IRBP S-Ag Mouse Optical coherence tomography Fundoscopy Histology Electroretinography 


  1. 1.
    Streilein JW (2003) Ocular immune privilege: the eye takes a dim but practical view of immunity and inflammation. J Leukoc Biol 74:179–185CrossRefGoogle Scholar
  2. 2.
    Caspi RR, Roberge FG, Nussenblatt RB (1987) Organ-resident, nonlymphoid cells suppress proliferation of autoimmune T-helper lymphocytes. Science 237:1029–1032CrossRefGoogle Scholar
  3. 3.
    Stein-Streilein J (2008) Immune regulation and the eye. Trends Immunol 29:548–554CrossRefGoogle Scholar
  4. 4.
    Taylor AW (2007) Ocular immunosuppressive microenvironment. Chem Immunol Allergy 92:71–85CrossRefGoogle Scholar
  5. 5.
    Zhou R, Horai R, Silver PB, Mattapallil MJ, Zarate-Blades CR, Chong WP, Chen J, Rigden RC, Villasmil R, Caspi RR (2012) The living eye “disarms” uncommitted autoreactive T cells by converting them to Foxp3(+) regulatory cells following local antigen recognition. J Immunol 188:1742–1750CrossRefGoogle Scholar
  6. 6.
    Zhou R, Horai R, Mattapallil MJ, Caspi RR (2011) A new look at immune privilege of the eye: dual role for the vision-related molecule retinoic acid. J Immunol 187:4170–4177CrossRefGoogle Scholar
  7. 7.
    Stein-Streilein J, Streilein JW (2002) Anterior chamber associated immune deviation (ACAID): regulation, biological relevance, and implications for therapy. Int Rev Immunol 21:123–152CrossRefGoogle Scholar
  8. 8.
    Kitaichi N, Namba K, Taylor AW (2005) Inducible immune regulation following autoimmune disease in the immune-privileged eye. J Leukoc Biol 77:496–502CrossRefGoogle Scholar
  9. 9.
    Caspi RR (2006) Ocular autoimmunity: the price of privilege? Immunol Rev 213:23–35CrossRefGoogle Scholar
  10. 10.
    Nussenblatt Rb WS (2004) Uveitis: fundamentals and clinical practice. Mosby (Elsevier), Philadelphia, PAGoogle Scholar
  11. 11.
    Caspi RR (2010) A look at autoimmunity and inflammation in the eye. J Clin Invest 120:3073–3083CrossRefGoogle Scholar
  12. 12.
    Agarwal RK, Silver PB, Caspi RR (2012) Rodent models of experimental autoimmune uveitis. Methods Mol Biol 900:443–469CrossRefGoogle Scholar
  13. 13.
    Fujimoto JG (2003) Optical coherence tomography for ultrahigh resolution in vivo imaging. Nat Biotechnol 21:1361–1367CrossRefGoogle Scholar
  14. 14.
    Chen J, Qian H, Horai R, Chan CC, Caspi RR (2013) Use of optical coherence tomography and electroretinography to evaluate retinal pathology in a mouse model of autoimmune uveitis. PLoS One 8:e63904CrossRefGoogle Scholar
  15. 15.
    Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, Hee MR, Flotte T, Gregory K, Puliafito CA, Et A (1991) Optical coherence tomography. Science 254:1178–1181CrossRefGoogle Scholar
  16. 16.
    Toth CA, Narayan DG, Boppart SA, Hee MR, Fujimoto JG, Birngruber R, Cain CP, Dicarlo CD, Roach WP (1997) A comparison of retinal morphology viewed by optical coherence tomography and by light microscopy. Arch Ophthalmol 115:1425–1428CrossRefGoogle Scholar
  17. 17.
    Drexler W, Morgner U, Ghanta RK, Kartner FX, Schuman JS, Fujimoto JG (2001) Ultrahigh-resolution ophthalmic optical coherence tomography. Nat Med 7:502–507CrossRefGoogle Scholar
  18. 18.
    Gallagher MJ, Yilmaz T, Cervantes-Castaneda RA, Foster CS (2007) The characteristic features of optical coherence tomography in posterior uveitis. Br J Ophthalmol 91:1680–1685CrossRefGoogle Scholar
  19. 19.
    Markomichelakis NN, Halkiadakis I, Pantelia E, Peponis V, Patelis A, Theodossiadis P, Theodossiadis G (2004) Patterns of macular edema in patients with uveitis: qualitative and quantitative assessment using optical coherence tomography. Ophthalmology 111:946–953CrossRefGoogle Scholar
  20. 20.
    Van Velthoven ME, Ongkosuwito JV, Verbraak FD, Schlingemann RO, De Smet MD (2006) Combined en-face optical coherence tomography and confocal ophthalmoscopy findings in active multifocal and serpiginous chorioretinitis. Am J Ophthalmol 141:972–975CrossRefGoogle Scholar
  21. 21.
    Chong GT, Lee RK (2012) Glaucoma versus red disease: imaging and glaucoma diagnosis. Curr Opin Ophthalmol 23:79–88CrossRefGoogle Scholar
  22. 22.
    Alam S, Zawadzki RJ, Choi S, Gerth C, Park SS, Morse L, Werner JS (2006) Clinical application of rapid serial fourier-domain optical coherence tomography for macular imaging. Ophthalmology 113:1425–1431CrossRefGoogle Scholar
  23. 23.
    Wojtkowski M, Srinivasan V, Fujimoto JG, Ko T, Schuman JS, Kowalczyk A, Duker JS (2005) Three-dimensional retinal imaging with high-speed ultrahigh-resolution optical coherence tomography. Ophthalmology 112:1734–1746CrossRefGoogle Scholar
  24. 24.
    Vincent A, Robson AG, Holder GE (2013) Pathognomonic (diagnostic) ERGs. A review and update. Retina 33:5–12CrossRefGoogle Scholar
  25. 25.
    Young B, Eggenberger E, Kaufman D (2012) Current electrophysiology in ophthalmology: a review. Curr Opin Ophthalmol 23:497–505CrossRefGoogle Scholar
  26. 26.
    Cortes LM, Avichezer D, Silver PB, Luger D, Mattapallil MJ, Chan CC, Caspi RR (2008) Inhibitory peptide analogs derived from a major uveitogenic epitope protect from antiretinal autoimmunity by inducing type 2 and regulatory T cells. J Leukoc Biol 84:577–585CrossRefGoogle Scholar
  27. 27.
    Chen J, Qian H, Horai R, Chan CC, Falick Y, Caspi RR (2013) Comparative analysis of induced vs. spontaneous models of autoimmune uveitis targeting the interphotoreceptor retinoid binding protein. PLoS One 8:e72161CrossRefGoogle Scholar
  28. 28.
    Silver PB, Chan CC, Wiggert B, Caspi RR (1999) The requirement for pertussis to induce EAU is strain-dependent: B10.RIII, but not B10.A mice, develop EAU and Th1 responses to IRBP without pertussis treatment. Invest Ophthalmol Vis Sci 40:2898–2905PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhouChina
  2. 2.Immunoregulation Section, Laboratory of ImmunologyNational Eye Institute, NEI, NIHBethesdaUSA

Personalised recommendations