Lviv clinical bulletin 2023, 2(42): 25-30

https://doi.org/10.25040/lkv2023.02.025

The Model of Experimental Non-Infectious Autoimmune Uveitis With Key Clinical Signs Manifestation Depending on the Severity Level

N. Kuryltsiv

Danylo Halytsky Lviv National Medical University

Introduction. Uveitis primarily affects young individuals and often leads to loss of productivity. Understanding the clinical, immunological, and morphological characteristics of this disease is of utmost importance and should be based on a thorough study of its developmental mechanisms. Therefore, the experimental modeling of uveitis in rabbits plays a significant role in studying its dynamics. There are numerous models of non-infectious autoimmune uveitis (NAU) available. However, previous publications did not address the question of the severity level of experimental NAU based on the type of used model or amount of antigen administered.

The aim of the study. To describe the model of experimental NAU exposing key clinical manifestations depending on the severity level.

Materials and methods. The study was conducted on 30 “Chinchilla” breed rabbits subdivided into two groups 15 animals each. NAU was induced  in both eyes by intravitreal injection of either insoluble (group I) or soluble (group II) sterile horse serum. On the days of animal withdrawal from the experiment (3, 7, 10, 14, and 21), the clinical manifestatioin of NAU was evaluated based on changes in the humidity of the anterior chamber and vitreous body. A quantitative assessment of clinical signs of NAU was conducted in both groups animals under investigation.

Results. From day 2, the clinical signs of NAU in two experimental groups demonstrated different degrees of severity of inflammation, with certain differences in the developmental dynamics. Namely, in group I, NAU was characterized by moderate and severe degrees of inflammation, while in group II, it was predominantly mild. In both groups, progress of intraocular inflammation was noted on days 3, 7, and 10, followed by a decrease in this process on the later phases of experiment. In comparison between two groups of rabbits concerning the dynamics of inflammatory clinical manifestations reflected in scores, a statistically significant differences were documented on all days of the experiment (p < 0.05).

Conclusions. An experimental model of non-infectious autoimmune uveitis is described, which manifests key clinical signs of this disease development depending on its severity level. These observations open a new possibilities for this model prospective use in clinical practice for diagnostic and prognostic purposes, as well as for the development of new protocols for endogenous uveitis effective treatment.

References

  1. Zbitneva SV. Morbidity of the population of Ukraine with diseases of the eye and its adnexal apparatus. Bulletin of Social Hygiene and Organizational Health Care of Ukraine. 2010;3:14-18 (Ukrainian)
  2. Altaweel MM, Holbrook JT, Jabs DA, Sugar EA.The Multicenter uveitis steroid treatment (MUST) trial: rationale, design and baseline characteristics. Am J Ophthalmol. 2010;149(4):550-561.
  3. Bansal S, Barathi VA, Iwata D, Agrawal Experimental autoimmune uveitis and other animal models of uveitis: AnUpdate. Indian J Ophthalmol. 2015;63(3):211-218.
  4. Calder VL, Lightman SL. Experimental autoimmune uveoretinitis (EAU) versus experimental allergic encephalomyelitis (EAE): a comparison of T cell-mediated mechanisms. Clin Exp Immunol. 1992;89(2):165-169.
  5. Caspi RR, Roberg FG, Chan CC, Wiggert B, Chader GJ, Rozenszajn LA et al. A newmodel of autoimmune disease. Experimental autoimmune uveoretinitis induced in mice with two different retinal antigens. J Immunol. 1988;140(5):1490-1495.
  6. Caspi RR. Understanding autoimmunity in the eye: From animalmodels to novel therapies. Discov Med. 2014;17:155-162.
  7. Chader GJ. Interphotoreceptor retinoid-binding protein (IRBP): a model protein for molecular biological and clinically relevant studies. Friedenwald lecture. Invest Ophthalmol Vis Sci. 1989;30(1):7-22.
  8. Davis JL, Madow B, Cornett J, Stratton R, Ditte Hess D et al. Scale for photographic grading of vitreous haze in uveitis. Am J Ophthalmol. 2010;150:637.
  9. De Smet MD, Chan CC. Regulation of ocular inflammation – what experimental and human studies have taught us. Prog Retin Eye Res. 2011;20(6):761-797.
  10. Deeg CA, Kaspers B, Gerhards H, Thurau SR, Wollanke B, Wildner G. Immune responses to retinal autoantigens and peptides in equine recurrent uveitis. Invest Ophthalmol Vis Sci. 2001;42(2):393-398.
  11. Eperon S, Balaskas K, Vaudaux J, Guex-Crosier Experimental uveitis can be maintained in rabbitsfor a period of six weeks after a safesensitization method. Current Eye Research. 2013;38(3):405-412.
  12. Faure JP. Autoimmunity and the retina. Curr Top Eye Res. 1980;2:215-302.
  13. Gasparin F, Takahashi BS, ScolariMR, Gasparin F, Pedra LS, Damico FM. Experimental models of autoimmune inflammatory ocular diseases. Arq Bras Oftalmol. 2012;75(2):143-147.
  14. Gery I, Mochizuki M, Nussenblat RB. Retinal specific antigens and the immunopatho-logic process they provoke. Prog Retin Res. 1986;5:75-109.
  15. Harimoto K, Ito M, Karasawa Y, Sakurai Y, Takeuchi M. Evaluation of mouse experimental autoimmune uveoretinitis by spectral domain optical coherence tomography. Br J Ophthalmol. 2014;98:808-812.
  16. Hennig M, Bauer D, Wasmuth S, Busch M, Walscheid K, Thanos S, Heiligenhaus A. Everolimus improves experimental autoimmune uveoretinitis. Exp Eye Res. 2012;105:43-52.
  17. Horai R, Silver PB, Agarwal RK, Mattapallil MJ, Natarajan K, Caspi RR et al. Breakdown of immune privilege and spontaneous autoimmunity in mice expressing a retina-specific T cell receptor. Int Immunol. 2010;22:21.
  18. Ioshimoto GL, Liber A, Zamudioigami T, Damico FM, Ventura DF. Experimental autoimmune uveitis in rabbits: clinical and functional evaluation. Investigative Ophthalmology & Visual Science. 2015;56(7):880-886.
  19. Jabs DA, Dick A, Doucette JT, Gupta A, Lightman S, McCluskey P et al. Interobserver agreement among uveitis experts on uveitic diagnoses: the Standard of uveitis nomenclature experience. Am J Ophthalmol. 2018;186:19-24.
  20. Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of uveitis nomenclature for reporting clinical data. Results of the first international workshop. Am J Ophthalmol. 2005;140(3):509-516.
  21. Kalsow CM, Wacker WB. Rabbit ocular and pineal autoimmune response to retina antigens. Curr Eye Res. 1986;5(8):579-586.
  22. McNeil R. Grading of ocular inflammation in uveitis: an overview. Eye. 2016;22(5):264-267.
  23. Peiffer RL,Pohm-Thorsen L, Corcoran К. Models in ophthalmology and vision research. The biology of the laboratory rabbit. 1994:409-433. Published online 2013.
  24. Peyman GA, Paque JT, Meisels HI, Bennett TO. Postoperative endophthalmitis: A comparison of methods for treatment and prophylaxis with gentamicin. Ophthalmic Surg. 1975;6(1):26-35.
  25. Rosenberg K, Feuer W, Davis J. Ocular complication of uveitis. Ophthalmol. 2004;111:2299-2306.
  26. Schewitz-Bowers LР, Lee RWJ, Dick DA. Immune mechanisms of intraocular inflammation. Exp Rev Ophthalmol. 2010;5(1):43-58.
  27. Tang J, Zhu W, Silver PB, Su SB, Chan CC, Caspi RR. Autoimmune uveitis elicited with antigen-pulsed dendritic cells has a distinct clinical signature and is driven by unique effector mechanisms: initial encounter with autoantigen defines disease phenotype. J Immunol. 2007;178(9):5578-5587.
  28. Xu H, Koch P, Chen M, Lau A, Reid DM, Forrester JV. A clinical grading system for retinal inflammation in the chronic model of experimental autoimmune uveoretinitis using digital fundus images. Exp Eye Res. 2008;87:319-326.
  29. Yang JM, Yun KA, Jeon J, Yang HY, Kim B, Jeong S et al. Multimodal evaluation of an interphotoreceptor retinoid-binding protein-induced mouse model of experimental autoimmune uveitis. Exp Mol Med. 2022;54(3):252-262.