We compared three mouse models of uveitis that target the interphotoreceptor retinoid binding protein (IRBP): (i) the "classical" model of experimental autoimmune uveitis (EAU) induced by immunization with IRBP; (ii) spontaneous uveitis in IRBP T cell receptor transgenic mice (R161H) and (iii) spontaneous uveitis in Autoimmune Regulator (AIRE)(-/-) mice.
We used this principle to design a strategy for gene therapy of experimental autoimmune uveitis, a cell-mediated autoimmune disease model for human uveitis induced with the uveitogenic interphotoreceptor retinoid-binding protein (IRBP).
Whereas previous studies mostly examined the effects of AR agonists on Th1-type immune responses, in this study, we compared their effect on Th17 and Th1 autoimmune responses in experimental autoimmune uveitis, a mouse model of human uveitis induced by immunization with the human interphotoreceptor retinoid-binding protein peptides 1-20.
The eye is an immunologically privileged organ whose Ags serve as targets for experimental autoimmune uveitis (EAU), a model for human uveitis.We used a hydrodynamic i.v. injection of naked DNA to express the uveitogenic retinal Ag interphotoreceptor retinoid-binding protein (IRBP) in the periphery, thus revoking its immune-privileged status.
Differences between normal and autoaggressive lymphocytes were identified in this study by analyzing peripheral blood derived lymphocytes (PBL) proteomes from the same case with interphotoreceptor retinoid binding protein induced uveitis sampled before (Day 0), during (Day 15), and after uveitic attack (Day 23).
In experimental autoimmune uveitis (EAU) induced by uveitogenic, interphotoreceptor retinoid-binding protein (IRBP)-specific T cells (tEAU) in mice, we have previously reported that high mobility group box 1 (HMGB1) released as a consequence of the direct interaction between IRBP-specific T cells and retinal parenchymal cells is an early and critical mediator in induction of intraocular inflammation.
TNF-α -308 GA/AA genotype was associated with a reduced risk of uveitis and better spinal function, while TNF-α -238 GA/AA genotype was associated with later age of onset and lower erythrocyte sedimentation rate (ESR).
Injection site pain (OR 6.14, 95% CI 1.15-32.74) and alopecia (OR 4.54, 95% CI 1.16-17.77) for adalimumab, chest pain (OR 6.01, 95% CI 1.35-26.77) for infliximab, and uveitis (OR 10.11, 95% CI 1.13-90.77) for etanercept were more likely to be reported in patients with each TNFα inhibitor than in those without, respectively.
We assayed aqueous humor (AH) samples from patients with Behçet's disease (BD), Vogt-Koyanagi-Harada (VKH) disease, and HLA-B27-associated uveitis and control patients for the proinflammatory cytokines IL-15, IL-17, interferon-γ and tumor necrosis factor-α and the immunosuppressive cytokine IL-10.
Methotrexate and the monoclonal antibody tumor necrosis factor inhibitors adalimumab and infliximab are recommended when systemic treatment is needed for the management of uveitis.
Indomethacin (IM) enhanced TNF production in all the eight TCC that were established from a patient with human T lymphotrophic virus type 1 uveitis or pulmonary sarcoidosis, and suppressed IL-6 production in six of the eight TCC, without affecting their low levels of PGE2 production.
Oxidative and nitrosative damage, tumor necrosis factor, and prostaglandin production have been involved in the pathogeny of uveitis and optic neuritis.
Despite clear differences in clinical course and outcome, MFCPU and PIC may still represent two manifestations of the same disease, given their similar genetic associations with IL10 and TNF loci, which are known to be associated with noninfectious uveitis and autoimmunity, in general.
To report the efficacy and tolerability of antitumour necrosis factor-alpha therapy (TNF inhibitors [TNFi]) in the management of non-infectious ocular inflammation, including uveitis and scleritis, in adult patients over an 8-year period.
We have recently reported that vitreous levels of IL-4, IL-17A, IL-22, IL-31, and TNFα are higher than the respective serum levels in proliferative diabetic retinopathy (PDR) patients, and that vitreous levels of these cytokines are higher in PDR than in other non-inflammatory vitreoretinal diseases or uveitis associated with sarcoidosis.
Tumor necrosis factor-α targeted therapies, the first-line recommended biologics in uveitis, have certainly led to remarkable results in patients with non-infectious uveitis.
Supporting a critical role for TNF activity during uveitis are reports that serum levels of TNFα correlate with disease status as well as the increasing evidence of therapeutic success of anti-TNF agents.
We investigate a hypothesized association between the TNF-alpha -857 C-to-T, -308 G-to-A, and the TNF-alpha -238 G-to-A SNPs and the presence of HLA-B27-associated uveitis.
Our results indicate that using a nonviral gene therapy strategy, the local self-production of monomeric TNF-alpha soluble receptors induces a local immunomodulation enabling the control of intraocular inflammation.