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

Abstract

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-value less than 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-value less than 0.05); on day 7th – 6.00 ± 0.20 nmol/l and 4.45 ± 0.30 nmol/l (p-value less than 0.05); on day 10th – 5.90 ± 0.40 nmol/l and 2.60 ± 0.40 nmol/l (p-value less than 0.05); on the 14th – 3.80 ± 0.40 nmol/l and 2.10 ± 0.10 nmol/l (p-value less than 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-value more than 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.