Abstract
As one of the leading causes of blindness worldwide, uveitis is an important disease. The exact pathogenesis of autoimmune uveitis is not entirely elucidated to date. Equine recurrent uveitis (ERU) represents the only spontaneous animal model for autoimmune uveitis in humans. As the metabolism of immune cells is an emerging field in research and gains more and more significance to take part in the pathogenesis of various diseases, we conducted experiments to investigate the metabolism of immune cells of ERU cases and healthy controls. To our knowledge, the link between a deviant immunometabolism and the pathogenesis of autoimmune uveitis was not investigated so far. We showed that PBMC of ERU cases had a more active metabolic phenotype in basal state by upregulating both the oxidative phosphorylation and the glycolytic pathway. We further revealed an increased compensatory glycolytic rate of PBMC and CD4+ T cells of ERU cases under mitochondrial stress conditions. These findings are in line with metabolic alterations of immune cells in other autoimmune diseases and basic research, where it was shown that activated immune cells have an increased need of energy and molecule demand for their effector function. We demonstrated a clear difference in the metabolic phenotypes of PBMC and, more specifically, CD4+ T cells of ERU cases and controls. These findings are another important step in understanding the pathogenesis of ERU and figuratively, human autoimmune uveitis.
Highlights
Equine recurrent uveitis (ERU) is an important disease in horses worldwide [1, 2], which, being untreated, eventually leads to loss of vision in the affected eyes [3]
By blocking mitochondrial respiration with rotenone/antimycin A (Rot/AA), the remaining oxygen consumption rates (OCR) resembles the non-mitochondrial oxygen consumption, which is likely caused by the activity of oxidoreductases and other enzymes and which remains as background in all other measurements addressed in the following
Peripheral blood mononuclear cells (PBMC) and CD4- cells of ERU cases consumed significantly more oxygen (** p ≤ 0.01) in basal state through their mitochondria, represented through a higher OCR level compared to controls
Summary
Equine recurrent uveitis (ERU) is an important disease in horses worldwide [1, 2], which, being untreated, eventually leads to loss of vision in the affected eyes [3] It is characterized by recurrent and painful episodes of inflammation, which are mainly caused by autoaggressive CD4+ T cells that migrate from the peripheral blood through the blood retinal barrier into the eye to attack and destroy retinal structures [1]. Patients with autoimmune uveitis receive long-term treatment with immune suppressants like high-dosed corticosteroids, cyclophosphamides or azathioprine or they are treated with antibodies against TNFa or IL-17 [reviewed in [14]] Unlike these human patients, horses affected by ERU are only treated for a few days when they experience an acute inflammatory episode and not in the quiescent stage of the disease [5, 15, 16], it is possible to examine immune reactions in the quiescent stage unaffected by long-term treatment
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