Vision impairment from corneal fibrosis is a common consequence of irregular corneal wound healing after injury. Intermediate-conductance calmodulin/calcium-activated K+ channels 3.1 (KCa3.1) play an important role in cell cycle progression and cellular proliferation. Proliferation and differentiation of corneal fibroblasts to myofibroblasts can lead to corneal fibrosis after injury. KCa3.1 has been shown in many non-ocular tissues to promote fibrosis, but its role in corneal fibrosis is still unknown. In this study, we characterized the expression KCa3.1 in the human cornea and its role in corneal wound healing in vivo using a KCa3.1 knockout (KCa3.1-/-) mouse model. Additionally, we tested the hypothesis that blockade of KCa3.1 by a selective KCa3.1 inhibitor, TRAM-34, could augment a novel interventional approach for controlling corneal fibrosis in our established in vitro model of corneal fibrosis. The expression of KCa3.1 gene and protein was analyzed in human and murine corneas. Primary human corneal fibroblast (HCF) cultures were used to examine the potential of TRAM-34 in treating corneal fibrosis by measuring levels of pro-fibrotic genes, proteins, and cellular migration using real-time quantitative qPCR, Western blotting, and scratch assay, respectively. Cytotoxicity of TRAM-34 was tested with trypan blue assay, and pro-fibrotic marker expression was tested in KCa3.1-/-. Expression of KCa3.1 mRNA and protein was detected in all three layers of the human cornea. The KCa3.1-/- mice demonstrated significantly reduced corneal fibrosis and expression of pro-fibrotic marker genes such as collagen I and α-smooth muscle actin (α-SMA), suggesting that KCa3.1 plays an important role corneal wound healing in vivo. Pharmacological treatment with TRAM-34 significantly attenuated corneal fibrosis in vitro, as demonstrated in HCFs by the inhibition TGFβ-mediated transcription of pro-fibrotic collagen I mRNA and α-SMA mRNA and protein expression (p<0.001). No evidence of cytotoxicity was observed. Our study suggests that KCa3.1 regulates corneal wound healing and that blockade of KCa3.1 by TRAM-34 offers a potential therapeutic strategy for developing therapies to cure corneal fibrosis in vivo.
Arthroscopic hip labral reconstruction is a complex procedure which is growing in use as indications, techniques, and surgical expertise advance.Graft selection is an important component of labral reconstruction based on relative advantages and disadvantages of available types of autografts and allografts.The ideal graft should mimic the native acetabular labrum form and function while also being affordable, readily available, and associated with low morbidity.High rates of patient satisfaction and positive patient-reported outcomes have been reported after labral reconstruction using several graft types.
Background Intraarticular corticosteroid injection is commonly used conservative treatment for glenohumeral osteoarthritis (OA). The purpose of this study was to investigate the clinical fate of symptomatic glenohumeral OA following intraarticular corticosteroid injection and to identify factors associated with undergoing shoulder arthroplasty. Methods Glenohumeral OA patients who had undergone at least one glenohumeral corticosteroid injection from 2012 to 2017 were identified. Data for demographics, comorbidities, number of injections, severity of radiographic arthritis, and subsequent treatment were collected up to February 2020. Data were analyzed to compare between patients who had eventually undergone shoulder arthroplasty and those who had not. Results A total of 311 shoulders (275 patients) were followed up for 3 to 8 years after the index injection. The mean age of patients was 64.7 years. There were 148 females, and 116 shoulders (37.3%) eventually underwent arthroplasty, 68 (21.9%) further injections only, 104 (33.4%) no further treatment, 14 (4.5%) a non-arthroplasty surgical procedure, and 9 (2.9%) were lost to follow up. Severity of radiographic arthritic changes, female sex, younger age, and nonsmoking status were found to be significantly associated with undergoing arthroplasty (p < 0.001, p = 0.014, p = 0.003, and p = 0.043, respectively). Conclusion Approximately one third of glenohumeral OA patients who had received an intraarticular corticosteroid injection eventually elected to undergo shoulder arthroplasty within 3 to 8 years of the injection. High-grade arthritic changes in radiographs, female gender, and younger age were found to be independent factors associated with undergoing arthroplasty. This information may be useful in counseling patients about their future clinical course. Level of Evidence: Level III Retrospective comparative study
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