Circulating S100A8/A9 Levels Reflect Intraocular Inflammation in Uveitis Patients.

Purpose: To investigate whether there is an association between circulating S100A8/A9 levels and uveitis activity.Methods: A total of 549 plasma samples were collected from uveitis patients and non-uveitic controls.Results: S100A8/A9 plasma levels were elevated in uveitis patients compared to non-uveitic controls (P < 0.001). S100A8/A9 plasma levels in patients with active acute anterior uveitis (AAU) were significantly elevated and remarkably decreased in parallel with the severity of intraocular inflammation after corticosteroid treatment (P < 0.001). S100A8/A9 plasma levels were also higher in AAU patients with ankylosing spondylitis (AS) than in patients without AS (P = 0.02). S100A8/A9 plasma levels were significantly increased in uveitis patients with elevated C-reactive protein (CRP, P = 0.004) or erythrocyte sedimentation rates (ESR, P = 0.049) levels compared to uveitis patients with normal CRP or ESR values.Conclusion: Circulating S100A8/A9 might be a useful biomarker for the measurement of intraocular inflammation.

Elevated Plasma Levels of Drebrin in Glaucoma Patients With Neurodegeneration.

Glaucoma is an optic neuropathy characterized by progressive degeneration of retinal ganglion cells (RGCs). Aberrations in several cytoskeletal proteins, such as tau have been implicated in the pathogenesis of neurodegenerative diseases, could be initiating factors in glaucoma progression and occurring prior to axon degeneration. Developmentally regulated brain protein (Drebrin or DBN1) is an evolutionarily conserved actin-binding protein playing a prominent role in neurons and is implicated in neurodegenerative diseases. However, the relationship between circulating DBN1 levels and RGC degeneration in glaucoma patients remains unclear. In our preliminary study, we detected drebrin protein in the plasma of glaucoma patients using proteomic analysis. Subsequently, we recruited a total of 232 patients including primary angle-closure glaucoma (PACG), primary open-angle glaucoma (POAG) and Posner-Schlossman syndrome (PS) and measured its DBN1 plasma levels. We observed elevated DBN1 plasma levels in patients with primary glaucoma but not in patients with PS compared to nonaxonopathic controls. Interestingly, in contrast to tau plasma levels increased in all groups of patients, elevated drebrin plasma levels correlated with retinal nerve fiber layer defect (RNFLD) in glaucoma patients. To further explore the expression of DBN1 in neurodegeneration, we conducted experiment of optic nerve crush (ONC) models, and observed increased expression of DBN1 in the serum as well as in the retina and then decreased after ONC. This result reinforces the potentiality of circulating DBN1 levels are increased in glaucoma patients with neurodegeneration. Taken together, our findings suggest that circulating DBN1 levels correlated with RNFLD and may reflect the severity of RGCs injury in glaucoma patients. Combining measurement of circulating drebrin and tau levels may be a useful indicator for monitoring progression of neurodegenerative diseases.

Integration of microRNA and mRNA expression profiles in the skin of systemic sclerosis patients.

MicroRNAs (miRNAs) play important roles in the fibrosis of systemic sclerosis (SSc). However, the underlying miRNA-mRNA regulatory network is not fully understood. A systemic investigation of the role of miRNAs would be very valuable for increasing our knowledge of the pathogenesis of SSc. Here, we combined miRNA and mRNA expression profiles and bioinformatics analyses and then performed validation experiments. we identified 21 miRNAs and 2698 mRNAs that were differentially expressed in SSc. Among these, 17 miRNAs and their 33 target mRNAs (55 miRNA-mRNA pairs) were involved in Toll-like receptor, transforming growth factor ß and Wnt signalling pathways. Validation experiments revealed that miR-146b, miR-130b, miR-21, miR-31 and miR-34a levels were higher whereas miR-145 levels were lower in SSc skin tissues and fibroblasts, normal fibroblasts and endothelial cells that were stimulated with SSc serum. ACVR2B, FZD2, FZD5 and SOX2 levels were increased in SSc skin fibroblasts, normal fibroblasts and endothelial cells that were stimulated with SSc serum. We did not identify any negative correlations among these miRNA-mRNA pairs. miR-21 was specifically expressed at higher levels in SSc serum. Six miRNAs and 4 mRNAs appear to play important roles in the pathogenesis of SSc are worth investigating in future functional studies.