Preventive effect of chrysin on experimental autoimmune uveitis triggered by injection of human IRBP peptide 1–20 in mice

Abstract

Uveitis is a common cause of blindness worldwide. Experimental autoimmune uveitis (EAU) is an animal model of noninfectious uveitis. Chrysin (5,7-dihydroxyflavone) is a member of the flavonoid family and has anti-inflammatory effects. We immunized C57BL/6J mice with human interphotoreceptor retinoid-binding protein peptide 1-20 to induce EAU. Chrysin was administered intragastrically at 25 mg/kg daily to the chrysin-treated mice from 3 days before immunization to 21 days after immunization. Vehicle was administered to the mice in the control group according to the same protocol. Lower clinical and histopathological scores, increased integrity of the blood-retinal barrier (BRB) and higher expression of tight junction proteins were observed in the chrysin-treated mice. Chrysin significantly decreased the proportions of Th1, Th17 and CD4CD3CD62L Th0 cells, and increased the proportion of Treg cells. Both macrophage infiltration and the expression of inducible nitric oxide synthase in the retina were efficiently inhibited by chrysin treatment. In chrysin-treated mice, the expression of interferon-γ, interleukin (IL)-17A, IL-6, IL-1β and tumor necrosis factor-α was reduced in the retina, whereas higher levels of transforming growth factor-β were detected. Furthermore, NF-κBp65 was downregulated after chrysin treatment. In conclusion, as an anti-inflammatory molecule, chrysin exerts a preventive effect on EAU by modulating the balance among helper T-cell subsets and suppressing ocular inflammation, thereby maintaining the integrity of the BRB.

Aryl Hydrocarbon Receptor Regulates Apoptosis and Inflammation in a Murine Model of Experimental Autoimmune Uveitis

“…When the BRB is destroyed, macrophages are recruited to attack intraocular tissues in EAU and increase the damage of photoreceptors and retina ( 7 , 41 ). Macrophages play dynamic roles in the pathogenesis of autoimmune-mediated inflammatory diseases and they are the main effector cells for tissue damage in EAU ( 48 ).…”

“…As described above, the pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β contribute to the recruitment and activation of M1 macrophages, leading to augmented ocular inflammation ( 7 ). We observed that TCDD treatment suppressed the levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β.…”

“…We observed that TCDD treatment suppressed the levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β. This anti-inflammatory effect of TCDD may be due to its modulation of macrophages/microglia, as the activated M1 subset accelerates inflammation and causes tissue damage by increasing the secretion of multiple pro-inflammatory cytokines such as TNF-α, IL-6, and the release of reactive oxygen species, resulting in the nitration of cytochrome c which is known to cause apoptosis ( 7 , 17 , 18 ). These findings indicate that the anti-inflammatory effect of AhR may contribute to its protection on BRB as well as the control of apoptosis.…”

“…Experimental autoimmune uveitis (EAU), an animal model of noninfectious uveitis, shares many common features in clinical and histological aspects with human uveitis ( 5 – 7 ). The most common concept of autoimmune uveitis is that it arises from an impairment of the immune privilege of the eye ( 8 – 10 ).…”

Small molecules targeting RORγt inhibit autoimmune disease by suppressing Th17 cell differentiation

“…Prior to inclusion in the experiments all immunized mice were inspected by slit lamp to ensure they had developed uveitis. The dose of 25 mg/kg was based on a similar dose regimen used in other studies in this field 14,21,22 . The control groups were injected with the solvent in the same manner.…”