These findings reveal that the levels of IL-23, IL-17, and IFN-gamma are elevated in BD patients with active uveitis, and they suggest that the IL-23/IL-17 pathway together with IFN-gamma is associated with the active intraocular inflammation in BD patients.
Idiopathic anterior uveitis, Behçet disease, and VKH syndrome are the most common entities of uveitis in China. Ocular toxoplasmosis, ocular histoplasmosis, and birdshot retinochoroidopathy are less common or absent in China.
Objective-Inflammation is closely linked to angiogenesis, and Toll-like receptors (TLRs) are the key mediators of inflammatory responses. However, the impact of TLRs on angiogenesis is incompletely understood. In this study, we determined the involvement of TLRs in angiogenesis. Methods and Results-In a mouse model of alkali-induced corneal neovascularization (CNV), we found that CNV was attenuated in TLR4 Ϫ/Ϫ but not TLR2 Ϫ/Ϫ mice. Further study revealed that the absence of TLR4 led to decreased production of proangiogenic factors in association with reduced accumulation of macrophages at the site of wounds, which was associated with reduced expression of high-mobility group box-1 (HMGB1) protein, an endogenous ligand for TLR4. Topical application of HMGB1 to the injured cornea promoted CNV with increased macrophage accumulation in wild-type mice but not in TLR4 Ϫ/Ϫ mice. HMGB1 treatment in vitro also promoted the production of proangiogenic factors by mouse macrophages in a TLR4-dependent manner. Furthermore, antagonists of HMGB1 and TLR4 reduced CNV and macrophage recruitment in the injured cornea of wild-type mice.
Conclusion-Our
The contribution of fiber alignment of scaffold on cellular mechanisms was evaluated by a comparative study of two different cells sourced from cornea. Electrospun scaffolds with similar composition and comparable fiber size were fabricated into randomly oriented and aligned scaffolds, which bear paralleled degradation of gelatin. Tensile test of wet scaffolds indicated that fiber alignment could influence its mechanical properties. Due to the unidirectional fiber orientation, aligned scaffold exhibited higher tensile modulus, higher break strength, and lower elongation at break than randomly oriented scaffold. The effect of fiber alignment on cells behavior was evaluated by cell morphology, specific protein expression, adhesion, and proliferation. Different corneal cells responded uniquely to fiber alignment of scaffold, keratocytes interacting more favorably on alignment scaffold and corneal epithelial cells more favorably on randomly oriented scaffold. These results confirmed that fiber alignment of scaffold would be benefit for cell proliferation if its contact guidance coincided with the cell shape and cytoskeletal tension. This finding is important to envisage an advanced composite scaffold that incorporates randomly oriented and aligned fibers for the growth and control of different cell types required for the successful development of corneal grafts by tissue engineering.
This study, for the first time, identified a strong association of an SNP of IL-23R, rs17375018, with BD. The results also suggested that both rs11209032 AA and rs17375018 GG of IL-23R are predisposing genotypes for BD and that the AGCG haplotype may provide protection against BD.
A significantly decreased frequency and diminished function of CD4(+)CD25(high) Treg cells is associated with active uveitis in patients with VKH syndrome. These results suggest that these dysfunctional CD4(+)CD25(high) Treg cells may play a role in the pathogenesis of uveitis in VKH syndrome.
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