Lviv clinical bulletin 2022, 3(39)-4(40): 33-39

Dynamics of Clinical Signs and Inflammatory Biomarker Neopterin Level in Blood Serum of Rabbits with Experimental Non-infectious Autoimmune Uveitis with Respect to Different Degrees of its Severity

N. Kuryltsiv1, O. Zborovska2, L. Velychko2, A. Khyrivskyi1

1Danylo Halytsky Lviv National Medical University 

2The Filatov Institute of Eye Diseases and Tissue Therapy of the National Academy of Medical Sciences of Ukraine

Introduction. Uveitis is an inflammatory condition involving iris, ciliary body and choroid of the eyebulb. Uveitis curretntly affects about two million people worldwide and is among five leading causes of blindness in the working population. Diagnosis of uveitis requires a number of investigations. As important biomarker in the diagnosis of uveitis can be used the detection of Neopterin (NP) in blood serum, since it is a stable metabolite and its increased level encompass activation of cellular immunity. It should be also noted that NP is present in blood serum and plasma, urine, tears, aqueous humor, vitreous body, other biological fluids and can be easily detected. According to literature data and our own investigations, the concentration of NP usually depends on the degree of activity of the pathological process, and its high concentration of NP is one of the main predictors of an unfavorable prognosis.

The aim of the study. To investigate the dynamics of clinical signs and inflammatory biomarker Neopterin level in blood serum of rabbits with experimental non-infectious autoimmune uveitis (NAU) considering varying degrees of severity.

Materials and methods. The experimental study was conducted on 30 rabbits of the “Chinchilla” breed, which were divided into two main groups (I and II), 15 animals in each. NAU was induced by intravitreal injection of an undiluted normal sterile horse serum to group I rabbits, while group II animals received diluted with the physiological solution serum in the proportion of 1:2. General sensitization was previously carried out with the same serum injected intravenously.

Results. The average level of NP in rabbits before the start of the experiment was 1.7 ± 0.2 nmol/l. It was considered the norm, since there is no information in the literature about the study of NP in healthy rabbits of the “Chinchilla” breed. In the reported research the severity of experimental NAU was estimated due to the concentration of the injected normal sterile horse serum intravitreally. As an additional proof of the development of NAU clinical picture was used the detection of Neopterin concentration in blood serum of rabbits. In both group animals the development of acute inflammation on days 3, 7, 10 and 14 of experiment the NP level was significantly higher compared to control (p < 0.05). However, in the I group animals with moderate and severe NAU, the level of NP was significantly higher than that in group II, in which uveitis was characterized by a mild course. Namely, on the 3rd day of experiment NP concentration in the I group animals was 5.60 ± 0.70 nmol/l, in the group II – 4.70 ± 0.60 nmol/l (p < 0.05); on day 7th – 6.00 ± 0.20 nmol/l and 4.45 ± 0.30 nmol/l (р < 0.05); on day 10th – 5.90 ± 0.40 nmol/l and 2.60 ± 0.40 nmol/l (p < 0.05); on the 14th – 3.80 ± 0.40 nmol/l and 2.10 ± 0.10 nmol/l (p < 0.05). On the day 21st, the NP concentration in both group animals did not differ statistically – estimated level 2.70 ± 0,30 nmol/l, (p > 0.05) – which apparently encompass the regression of inflammatory changes in the eye.

Conclusions. A correlation between the severity of experimental non-infectious autoimmune uveitis with concentration of inflammatory biomarker neopterin in blood serum was investigated in rabbits. NP level in all experimental animals was elevated and statistically different in comparison to NP control levels on days 3rd, 7th, 10th and 14th day of experiment. In the group of animals with a more severe course of uveitis, a significantly higher level of NP was noted compared to animals with a milder course of NAU. This observation confirms the immune response to inflammation and the stability of NP biomarker in blood serum. The dynamics of this biomarker levels in rabbits of two experimental groups has a correlation with the dynamics of clinical changes. Detection of the inflammatory biomarker Neopterinin in blood serum can be used as a criterion for assessement the severity of non-infectious autoimmune uveitis, its course and, probably, prognosis.


  1. Kuryltsiv NB, Zborovska OV. Neopterin, a promising biomarker for the diagnosis of intraocular inflammation. J Ophthalmol. 2021;3:55-60) (Ukrainian)
  2. Miheiceva IM, Bondarenko NV, Kolomijchuk SH, Kuryltsiv NB. The level of neopterin in the anterior segment of the eye in experimental uveitis aggravated by ocular hypertension under the condition of exposure to carnosinedipeptide. J Ophthalmol. 2021;5:64-70 (Ukrainian)
  3. Bansal R, Gupta A. Protein Biomarkers in Uveitis. Front Immunol. 2020;11:1-13.
  4. BEST (Biomarkers, EndpointS, and other Tools) Resource: FDANIH Biomarker Working Group; 2021:54 p.
  5. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89-95.
  6. Cholkar K, Dasari SR, Pal D, Mitra AK. Eye: anatomy, physiology and barriers to drug delivery. Ocular transporters and receptors. Woodhead Publishing. 2013;4:1-36.
  7. Deschenes J, Murray PI,Rao NA, Nussenblatt RB. International Uveitis Study Group (IUSG): clinical classification of uveitis. Ocul Immunol Inflamm. 2008;16(1):1-2.
  8. Durrani OM, Tehrani NN, Marr JE, Moradi P, Stavrou P, Murray PI. Degree, duration, and causes of visual loss in uveitis. Br J Ophthalmol. 2004;88:1159-1162.
  9. Foster CS, Kothari S, Anesi SD, Vitale AT, Chu D,Metzinger JL et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016;61(1):1-17.
  10. Hsu YR, Huang JC, Tao Y, Kaburaki T, Lee, Lin TC et al. Noninfectious uveitis in the Asia-Pacificregion. Eye (Lond). 2019;3(1):66-77.
  11. 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.
  12. Krishna U, Ajanaku D, Denniston AK, Gkika T. Uveitis: a sight-threatening disease which can impact all systems. Postgrad Med J. 2017;93:766-773.
  13. Lohoff M. Mak TW. Roles of interferon-regulatory factors in Thelper-cell differentiation. Nat Rev Immunol. 2005;5(2):125-135.
  14. Muller MM, Curtius HC, Herold M, Huber CH. Neopterin in clinical practice. Clin Chim Acta.1991;201:1-16.
  15. Muñoz-Fernández S, Martín-Mola E. Uveitis. Best Pract Res Clin Rheumatol. 2006;20:487-505.
  16. Murr C, Widner B, Wirleitner D. Fuchs neopterinas a marker for immune system activation. Curr Drug Metab. 2002;3:175-187.
  17. Ooi KGJ, Galatowicz G, Calder VL, Lightman SL. Cytokines and chemokines in uveitis – isthere a correlation with clinical phenotype. Clin Med Res. 2006;4(4):294-309.
  18. Pingle SK, Tumane RG, Jawade AA. Neopterin: biomarker of cell-mediated immunity and potent usage as biomarker in silicosis and other occupational diseases. Indian J Occup Environ Med. 2008;12(3):107-111.
  19. Rosenbaum JT, Bodaghi B, Couto C, Zierhut M, Acharya N, Pavesio C et al. New observations and emerging ideas in diagnosis and management of non-infectious uveitis: a review. Semin Arthritis Rheum. 2019;49(3):438-445.
  20. Rothova A, Buitenhuis HJ, Meenken C, Brinkman CJ, Linssen A, Alberts C et al. Uveitis and systemic disease. Br J Ophthalmol. 1992;76:137-141.
  21. Rothova A, Suttorp-van Schulten MS, Frits Treffers W, Kijlstra A. Causes and frequency of blindness in patients with intraocular inflammatory disease. Br J Ophthalmol. 1996;80(4):332-336.
  22. Takase H, Sugita S, Taguchi C, Mochizuki M. Capacity of ocular infiltrating T helper type 1 cells of patients with non-infectious uveitis to produce chemokines. Br J Ophthalmol. 2006;90(6):765-768.
  23. Tamhane1 M, Cabrera-Ghayouri S, Abelian G, Viswanath V. Review of Biomarkers in Ocular Matrices: Challenges and Opportunities. Pharm Res. 2019;36(40):39-74.
  24. Trusko B, Thorne J, Jabs D, Belfort R, Dick A, Gangaputra S et al. Standardization of Uveitis Nomenclature Working Group. The SUN Project. Development of a clinical evidence base utilizing informatics tools and techniques. Methods Inf Med. 2013;52:259-265.
  25. Tsirouki T, Dastiridou A, Symeonidis C, Tounakaki O, Brazitikou I, Kalogeropoulos C et al. A focus on the epidemiology of uveitis. Ocul Immunol Inflamm. 2018;26:2-16.
  26. Zierhut M, Deuter C, Murray FI. Classification of uveitis – current guidelines. European Ophthalmic Review. 2007;77-78.