Bradycardia-dependent conduction block of the atrial tissue in a patient after double-chamber implantable cardioverter defibrillator implantation.

Seldom are reports of phase 4 block or bradycardia-dependent conduction block in atrial tissue found in the literature. Here, we describe the case of a patient with sick sinus syndrome with Torsade de Pointes who, following the implantation of a double-chamber implantable cardioverter defibrillator, developed intra-atrial bradycardia-dependent conduction block. The patient's optimal pacing parameters were achieved by raising the rate.

Intraocular pressure measurement and association with corneal biomechanics in patients underwent Descemet's stripping with endothelial keratoplasty: a comparative study.

Purpose: To compare corneal biomechanical properties and intraocular pressure (IOP) measurements in patients who underwent Descemet's stripping with endothelial keratoplasty (DSEK) with those of the follow healthy eyes. Methods: In this retrospective comparative study, a total of 35 eyes of 35 patients who underwent DSEK by a single surgeon from 2015.02 to 2019.12 were enrolled along with their fellow healthy eyes. Corneal biomechanical parameters were assessed at least 3 months post-DSEK using Corneal Visualization Scheimpflug Technology (CST). IOP was measured by CST, Goldmann applanation tonometry (GAT), and MacKay-Marg tonometer. Results: Central corneal thickness (CCT) and stiffness parameter at first applanation (SP-A1) were significantly increased after DSEK when compared to the fellow eyes. In DSEK eyes, biomechanically-corrected intraocular pressure (bIOP) and MacKay-Marg IOP correlated significantly with GAT IOP measurements, with bIOP showed the lowest IOP values. All the IOP values did not correlate with CCT. However, GAT-IOP and MacKay-Marg IOP showed a positive correlation with SP-A1. Conclusion: The corneal stiffness increased after DSEK. Central corneal thickness may have less influence than corneal biomechanics on IOP measurements in eyes after DSEK. Biomechanically-corrected IOP obtained by CST seemed to be lower than other tonometry techniques in DSEK eyes, perhaps because of correction for corneal stiffness, CCT and age.

Sustained release of brimonidine from conjunctival sac insert to reduce intraocular pressure for glaucoma treatment.

BACKGROUND: Glaucoma is one of the major irreversible blinding eye diseases in the world. Reducing intraocular pressure (IOP) is the primary treatment option, and taking eye drops daily is the common method. However, short drug duration and poor bioavailability of eye drops may lead to unsatisfied therapeutic effects and inadequate patient compliance. METHODS: A brimonidine-loaded silicone rubber insert (BRI@SR@PT) was prepared by loading brimonidine into a surface-modified silicone rubber ring, followed by polydopamine/thermoplastic polyurethane coatings. The physical properties, in vitro cytocompatibility and drug release of BRI@SR@PT were investigated. The BRI@SR@PT was administrated in the conjunctival sac of rabbit eyes, and its in vivo drug release, IOP-lowering efficacy and biosafety were assessed. RESULTS: The BRI@SR@PT presented great thermal stability and excellent elasticity. The BRI@SR@PT was able to release BRI sustainably for 28 days with little toxicity in vitro. Compared to BRI eye drops, the BRI@SR@PT effectively lowered IOP for 21 days based on the sustained BRI release with great biosafety when administrated in conjunctival sac of rabbit eyes in a noninvasive fashion. CONCLUSIONS: The conjunctival sac insert (BRI@SR@PT), as a promising drug-delivery platform, may provide a sustained IOP-lowering treatment for patients with ocular hypertension or glaucoma, without the need for invasive procedures.

A highly selective inhibitor of discoidin domain receptor-1 (DDR1-IN-1) protects corneal epithelial cells from YAP/ACSL4-mediated ferroptosis in dry eye.

BACKGROUND AND PURPOSE: This study investigated the involvement of discoidin domain receptor (DDR) in dry eye and assessed the potential of specific DDR inhibitors as a therapeutic strategy for dry eye by exploring the underlying mechanism. EXPERIMENTAL APPROACH: Dry eye was induced in Wistar rats by applying 0.2% benzalkonium chloride (BAC), after which rats were treated topically for 7 days with DDR1-IN-1, a selective inhibitor of DDR1. Clinical manifestations of dry eye were assessed on Day-7 post-treatment. Histological evaluation of corneal damage was performed using haematoxylin and eosin (H&E) staining. In vitro, immortalized human corneal epithelial cells (HCECs) exposed to hyperosmotic stress (HS) were treated with varying doses of DDR1-IN-1 for 24 h. The levels of lipid peroxidation in dry eye corneas or HS-stimulated HCECs were assessed. Protein levels of DDR1/DDR2 and related pathways were detected by western blotting. The cellular distribution of acyl-CoA synthetase long chain family member 4 (ACSL4) and Yes-associated protein (YAP) was evaluated using immunohistochemistry or immunofluorescent staining. KEY RESULTS: In dry eye corneas, only DDR1 expression was significantly up-regulated compared with normal controls. DDR1-IN-1 treatment significantly alleviated dry eye symptoms in vivo. The treatment remarkably reduced lipid hydroperoxide (LPO) levels and suppressed the expression of ferroptosis markers, particularly ACSL4. Overexpression or reactivation of YAP diminished the protective effects of DDR1-IN-1, indicating the involvement of the Hippo/YAP pathway in DDR1-targeted therapeutic effects. CONCLUSIONS AND IMPLICATIONS: This study confirms the significance of DDR1 in dry eye and highlights the potential of selective DDR1 inhibitor(s) for dry eye treatment.

Associations between genetically predicted TIMP-3 levels and risk of venous thromboembolism: A two sample Mendelian randomization study.

TIMP metallopeptidase inhibitor 3 (TIMP-3) may contribute to the pathogenesis of venous thromboembolism (VTE). However, few studies have investigated the effect of TIMP-3 on VTE. Therefore, a two-sample Mendelian randomization (MR) analysis was conducted to investigate the association between TIMP-3 levels and VTE. Seven independent single-nucleotide polymorphisms (SNPs) for TIMP-3 levels were obtained from a published genome-wide association study (the KORA Consortium, including 997 Europeans). We obtained outcome datasets for VTE, pulmonary embolism (PE), and deep vein thrombosis (DVT) from the FinnGen Consortium. The primary analytical method used in the MR analysis was the inverse variance weighted (IVW) method. To enhance the robustness of the MR results, some other MR methods including weighted median, MR-Egger, and MR-PRESSO were conducted. Moreover, several sensitivity analyses were performed to identify potential horizontal pleiotropy and heterogeneity. In primary IVW MR analyses, per log increase in genetically predicted TIMP-3 levels were positively associated with the incidence of VTE (odds ratio [OR], 1.03; 95 % confidence interval (CI), 1.01, 1.06; P = 0.010), PE (OR, 1.04; 95 % CI, 1.01, 1.08; P = 0.009), and DVT (OR, 1.06; 95 % CI, 1.02, 1.10; P= 0.003). The results of the weighted median, MR-Egger, and MR-PRESSO were similar to the main findings. No unbalanced pleiotropy or heterogeneity was observed. The study suggests that genetically predicted high levels of TIMP-3 may be associated with an increased risk of VTE. These findings indicate that strategies targeting TIMP-3 may provide a basis for the prevention and treatment of VTE. Further investigation is required to clarify this potential mechanism.

Dendritic-cell-targeting virus-like particles as potent mRNA vaccine carriers.

Messenger RNA vaccines lack specificity for dendritic cells (DCs)-the most effective cells at antigen presentation. Here we report the design and performance of a DC-targeting virus-like particle pseudotyped with an engineered Sindbis-virus glycoprotein that recognizes a surface protein on DCs, and packaging mRNA encoding for the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or for the glycoproteins B and D of herpes simplex virus 1. Injection of the DC-targeting SARS-CoV-2 mRNA vaccine in the footpad of mice led to substantially higher and durable antigen-specific immunoglobulin-G titres and cellular immune responses than untargeted virus-like particles and lipid-nanoparticle formulations. The vaccines also protected the mice from infection with SARS-CoV-2 or with herpes simplex virus 1. Virus-like particles with preferential uptake by DCs may facilitate the development of potent prophylactic and therapeutic vaccines.

Long noncoding RNA ZFAS1: A novel anti-apoptotic target in Fuchs endothelial corneal dystrophy.

Fuchs endothelial corneal dystrophy (FECD) is the leading cause of endothelial keratoplasty without efficacious drug treatment. Recent studies have emphasized the involvement of epigenetic regulation in FECD development. Long non-coding RNAs (lncRNAs) are recognized as crucial epigenetic regulators in diverse cellular processes and ocular diseases. In this study, we revealed the expression patterns of lncRNAs using high-throughput sequencing technology in FECD mouse model, and identified 979 significantly dysregulated lncRNAs. By comparing the data from FECD human cell model, we obtained a series of homologous lncRNAs with similar expression patterns, and revealed that these homologous lncRNAs were enriched in FECD related biological functions, with apoptosis (mmu04210) showing the highest enrichment score. In addition, we investigated the role of lncRNA zinc finger antisense 1 (ZFAS1) in apoptotic process. This study would broaden our understanding of epigenetic regulation in FECD development, and provide potential anti-apoptotic targets for FECD therapy.

Arthroscopic Excision of Posterior Cruciate Ligament Cysts Using a Double Posteromedial Approach.

Cruciate ligament cysts of the knee are a rare condition. Posterior cruciate ligament cysts of the knee are less common than anterior cruciate ligament cysts. In patients with asymptomatic isolated cruciate ligament cysts of the knee, conservative treatment is recommended. Symptomatic cruciate ligament cysts of the knee are mostly manifested as knee hyperflexion pain, straightening pain, knee discomfort after standing for a long time or walking for a long time, etc., which seriously affects the quality of life, surgical treatment can be performed. The surgical treatments can be divided into ultrasound-guided cyst puncture and fluid extraction procedure and arthroscopic cystectomy. Cysts are mostly lobulated with a multi-layer cyst wall, cyst fluid extraction does not remove the cyst wall completely but simply extracts cyst fluid, leading to a high recurrence rate. Arthroscopic surgery can completely remove the cyst wall with little trauma, a low recurrence rate, and fast postoperative recovery, so arthroscopic resection is the most common and preferred method of treatment. Since posterior cruciate ligament cysts mostly occur posterior to the ligament, we remove the cyst wall by adding a double posteromedial approach to the knee joint, and the cyst wall is removed under direct vision, which is simple to operate, the cyst wall is completely cleared, the trauma is small, the postoperative recovery is fast, and there is no recurrence. Here, 8 posterior cruciate ligament cysts were removed with complete postoperative symptom relief, no surgical complications, and no recurrence at 1-year follow-up.

Integrative analysis of gene expression datasets in corneal endothelium samples of Fuchs endothelial corneal dystrophy.

FECD is an age-related progressive ocular disorder characterized by the gradual loss of corneal endothelial cells. Although the exact pathogenesis of FECD remains incompletely understood, differentially expressed genes in the corneal endothelium of FECD patients compared to controls have been reported in several studies. However, a consensus regarding consistently affected genes in FECD has not been established. To address this issue, we conducted a comprehensive meta-analysis incorporating five studies with data that met our predefined inclusion criteria. The combined dataset included 41 FECD patients and 26 controls. We conducted study-level analyses, followed by a meta-analysis, and subsequent functional enrichment analysis targeting the topmost DEGs. Our findings revealed a total of 1537 consistently dysregulated genes in the corneal endothelium of FECD patients. Notably, only 14.6% (224/1537) of these DEGs had been previously identified as statistically significant in individual datasets. Functional enrichment analysis revealed that the upregulated DEGs were significantly enriched in immune-related signaling pathways, with a particularly high enrichment in "The NLRP3 inflammasome" and "Inflammasomes" pathways. In conclusion, we successfully identify a set of consistently dysregulated genes in FECD, which are associated with both established and novel biological pathways. This study highlights the importance of further investigating the role of inflammasomes in FECD pathogenesis and exploring strategies to modulate inflammasome activation for the management of this debilitating condition.

In vivo CRISPR gene editing in patients with herpetic stromal keratitis.

In vivo CRISPR gene therapy holds large clinical potential, but the safety and efficacy remain largely unknown. Here, we injected a single dose of herpes simplex virus 1 (HSV-1)-targeting CRISPR formulation in the cornea of three patients with severe refractory herpetic stromal keratitis (HSK) during corneal transplantation. Our study is an investigator-initiated, open-label, single-arm, non-randomized interventional trial at a single center (NCT04560790). We found neither detectable CRISPR-induced off-target cleavages by GUIDE-seq nor systemic adverse events for 18 months on average in all three patients. The HSV-1 remained undetectable during the study. Our preliminary clinical results suggest that in vivo gene editing targeting the HSV-1 genome holds acceptable safety as a potential therapy for HSK.

Gasdermin D affects aortic vascular smooth muscle cell pyroptosis and Ang II-induced vascular remodeling.

Vascular smooth muscle cells (VSMCs) are primarily responsible for vasoconstriction and the regulation of blood pressure1. Pyroptosis, a particular form of regulated cell death, is involved in multiple vascular injuries, including hypertensive vascular dysfunction. This pyroptotic cell death is mediated by the pore-forming protein of Gasdermin D (GSDMD). This study was designed to examine the direct effect of GSDMD on smooth muscle cell pyroptosis and vascular remodeling. Findings revealed that GSDMD was activated in Angiotensin (Ang) II- treated aortas. We then showed that genetic deletion of Gsdmd reduced vascular remodeling and aorta pyroptosis induced by Ang II in vivo. Aberrant expression of GSDMD by recombinant AAV9 virus carrying Gsdmd cDNA aggravated the level of pyroptosis in aortas of Ang II mice. Gain- and loss-of- function analysis further confirmed that GSDMD regulated the pyroptosis of murine aortic vascular smooth muscle cells (MOVAS) in an in vitro model of tumor necrosis factor (TNF)-α treatment, which was achieved by transfecting expressing plasmid or siRNA, respectively. Overall, this study provided evidence supporting the active involvement of GSDMD in smooth muscle cell pyroptosis and Ang II-induced mice vascular injury. This finding lends credence to GSDMD as a potential therapeutic target for hypertensive vascular remodeling via inhibiting pyroptosis.

Sustained release of brimonidine from polydimethylsiloxane-coating silicone rubber implant to reduce intraocular pressure in glaucoma.

Glaucoma is the leading cause of irreversible blindness, affecting 111 million people by 2040 worldwide. Intraocular pressure (IOP) is the only controllable risk factor for the disease and current treatment options seek to reduce IOP via daily taking eye drops. However, shortcomings of eye drops, such as poor bioavailability and unsatisfied therapeutic effects, may lead to inadequate patient compliance. In this study, an effective brimonidine (BRI)-loaded silicone rubber (SR) implant coated with polydimethylsiloxane (BRI@SR@PDMS) is designed and fully investigated for IOP reduction treatment. The in vitro BRI release from BRI@SR@PDMS implant reveals a more sustainable trend lasting over 1 month, with a gradually declined immediate drug concentration. The carrier materials show no cytotoxicity on human corneal epithelial cells and mice corneal epithelial cells in vitro. After administrated into rabbit's conjunctival sac, the BRI@SR@PDMS implant releases BRI in a sustained fashion and effectively reduces IOP for 18 days with great biosafety. In contrast, BRI eye drops only maintain IOP-lowering effect for 6 h. Therefore, as a substitute of eye drops, the BRI@SR@PDMS implant can be applied as a promising non-invasive platform to achieve long-term IOP-lowering in patients suffering from ocular hypertension or glaucoma.

3% diquafosol sodium eye drops in Chinese patients with dry eye: a phase IV study.

Introduction: The efficacy and safety of 3% diquafosol sodium eye drops in Chinese patients with dry eye in the real-world setting remains unclear. Methods: 3099 patients with dry eye symptoms were screened according to Asia Dry Eye Society latest recommendation. Among them, 3000 patients were enrolled for a phase IV study. We followed up with multiple clinical characteristics including corneal fluorescein staining, tear break up time, Schirmer's tests, visual acuity, intraocular pressure, and others. The follow ups were performed at baseline, 2 weeks and 4 weeks after treatment. Results: Based on the results of corneal fluorescein staining and tear break up time, all age and gender subgroups exhibited obvious alleviation of the symptoms among the patients with dry eye, and the data in elderly group showed the most significant alleviation. All the adverse drug reactions (ADRs, 6.17%) were recorded, among which 6% local ocular ADRs were included. Meanwhile, mild ADRs (91.8%) accounted for the most. Most of the ADRs (89.75%) got a quick and full recovery, with an average time at 15.6 days. 1.37% of patients dropped out of the study due to ADRs. Discussion: The use of 3% diquafosol sodium eye drop is effective and safe in the treatment of dry eye, with a low incidence of ADRs showing mild symptoms. This trial was registered at Chinese Clinical Trial Registry ID: ChiCTR1900021999 (Registration Date: 19/03/2019).

Effect of eye rubbing on corneal biomechanical properties in myopia and emmetropia.

Purpose: To investigate short-term changes in corneal biomechanical properties caused by eye rubbing in myopia and emmetropia and compare the different responses between the two groups. Methods: This was a prospective observational study of 57 eyes of 57 healthy subjects aged 45 years and younger. The participants were divided into myopia and emmetropia groups. All the subjects underwent eye rubbing by the same investigator using the same technique. Biomechanical parameters were recorded using the Corvis ST device before and after 1 min of eye rubbing. One week later, all the participants underwent the test again. Statistical methods were employed to compare the differences between the data from before and after the 1 min of eye rubbing and demonstrate the different responses of the two groups. Results: After 1 min of eye rubbing, smaller SP-A1 (p < 0.001), higher deformation and deflection amplitudes (p < 0.001, p = 0.012), higher peak distances (p < 0.001), earlier A1 times (p < 0.001), faster velocities (p < 0.001), and lower maximum inverse radii (p = 0.004) were observed. According to the automatic linear modeling analysis, the refractive states (B = -5.236, p = 0.010) and biomechanically corrected intraocular pressure (bIOP) (B = 0.196, p = 0.016) had influenced a decrease in the stiffness parameter at the first applanation (SP-A1). The central corneal thickness (CCT) had decreased only in the myopia group (p = 0.039). The change of SP-A1 in amplitude was larger in the myopia group than in the emmetropia group (p < 0.001). All the parameters returned to the baseline level 1 week later. Conclusion: Eye rubbing appears to alter corneal biomechanical properties temporarily and make the cornea softer, especially for myopic young patients.

The Workability and Mechanical Performance of Fly Ash Cenosphere-Desert Sand Ceramsite Concrete: An Experimental Study and Analysis.

In order to alleviate the shortage of sand resources for construction, make full use of industrial waste and promote the development of green lightweight aggregate concrete in the desert and surrounding areas, this paper proposes a new lightweight ceramsite concrete, fly ash cenospheres and desert sand ceramsite concrete (FDCC). An orthogonal test was conducted to analyze the effects of the desert sand (DS) replacing ratio, fly ash cenosphere (FAC) replacing ratio and polymer emulsion (PLE) addition on the damage patterns, slump, apparent density and compressive strength of the FDCC. The results showed that the most influential factors for the slump, apparent density and compressive strength of the FDCC were the FAC replacing ratio, FAC replacing ratio and DS replacing ratio, respectively. Meanwhile, the PLE addition had little effect on the workability or mechanical performance of the FDCC. With the increase in the DS replacing ratio, the slump decreased rapidly and the compressive strength reached its peak value, increasing by 20.6% when the DS replacing ratio was 20%. With the increase in the FAC replacing ratio, the slump increased by 106%, the apparent density decreased gradually and the compressive decreased and then increased, reaching its lowest value when the FAC replacing ratio was 20%. According to the synthetic evaluation analysis, the optimum DS replacing ratio, FAC replacing ratio and PLE addition of the FDCC were 20%, 30% and 1%, respectively.

miRNA­92a inhibits vascular smooth muscle cell phenotypic modulation and may help prevent in­stent restenosis.

The modulation of vascular smooth muscle cell (VSMC) phenotype during cellular proliferation and migration may represent a potential therapeutic approach for vascular intimal hyperplasia prevention. However, the precise role of this process in VSMC biology and remodeling remains unclear. In the present study, western blotting, PCR, MTT and Transwell assays were used to analyze related protein and mRNA expression, cell viability and cell migration, respectively. It was demonstrated that miR­92a modulated VSMCs into a synthetic phenotype via the Kruppel­like factor 4 (KLF4) pathway. Targeting microRNA (miRNA/miR)­92a in VSMCs using a KLF4 inhibitor suppressed the synthetic phenotype and inhibited VSMC proliferation and migration. To further confirm this finding, the expression levels of miR­92a were measured in patients undergoing coronary artery intervention. The serum miR­92a expression levels were significantly higher in patients with in­stent restenosis (ISR) compared with those in patients without ISR, whereas KLF4 expression was significantly reduced in the non­ISR group. Bioinformatic analysis and promoter­luciferase reporter assays were used to examine the regulatory mechanisms underlying KLF4 expression. KLF4 was demonstrated to be transcriptionally upregulated by miR­92a in VSMCs. miRNA transfection was also performed to regulate the level of miR­92a expression. miR­92a overexpression inhibited VSMC proliferation and migration, and also increased the mRNA and protein expression levels of certain differentiated VSMC­related genes. Finally, miR­92a inhibition promoted the proliferation and migration of VSMCs, which could be reversed using a KLF4 inhibitor. Collectively, these results indicated that the local delivery of a KLF4 inhibitor may act as a novel therapeutic option for the prevention of ISR.

Clinical Investigation of the Safety and Efficacy of Low-temperature Plasma as an Adjuvant Treatment for Mild to Moderate Fungal Keratitis: A Pilot Study.

PURPOSE: This pilot study assessed the safety and efficacy of low-temperature plasma (LTP) as an adjuvant treatment for mild to moderate fungal keratitis (FK). METHODS: Thirty FK patients were randomized into LTP (n = 15) and control (n = 15) groups. Patients were followed up for 3 months. The best-corrected visual acuity (BCVA), ulcer size, and hypopyon height were measured; healing time or complications were documented and compared. RESULTS: More patients in the LTP group healed completely (11/15 in 48 days) compared with the control group (4/15 in 59.5 days), and those patients had a deeper initial ulcer depth and exhibited better BCVA improvements. Four patients failed after LTP treatment due to perforation, increased inflammatory infiltration, or hypopyon; those with more hypopyon were more likely to fail. CONCLUSIONS: LTP could be a promising adjuvant therapy to topical antifungal drugs for mild to moderate FK.

Stability and Function of Extracellular Vesicles Derived from Immortalized Human Corneal Stromal Stem Cells: A Proof of Concept Study.

With significant advancement and development of extracellular vesicle (EV)-based therapies, there is a growing need to understand how their storage affects their physical and functional characteristics. EVs were isolated from the conditioned medium of a corneal stromal stem cell line (imCSSC) using Total Exosome isolation kit (TEI) and ultracentrifugation (UC) combined protocol. Purified EVs were stored at 4°C, - 80°C, room temperature (RT) after lyophilization with or without trehalose for 4 weeks. EVs stored at - 80°C and RT (lyophilization with trehalose) demonstrated a comparable morphology, while the freeze-dried samples without trehalose showed aggregation and degradation under a transmission electron microscope (TEM). Lyophilized samples without trehalose demonstrated a decreased particle concentration, recovery rate and protein concentration, which was remediated by the addition of trehalose. EVs stored at - 80℃ showed no change in the protein expression of CD9, CD63, and CD81. Regardless of the storage condition, all EV samples investigated reduced inflammation, as well as inhibited expression of fibrotic markers in vitro. Lyophilization of EVs with trehalose was a feasible storage method that retained the physical property and in vitro biological activities of EVs after 4 weeks of storage, while - 80°C offered the best retention of imCSSC-derived EV physical properties. For the first time, this data demonstrated a practical and translatable method for the storage of CSSC-derived EVs for clinical use.

Generation of Functional Immortalized Human Corneal Stromal Stem Cells.

In addition to their therapeutic potential in regenerative medicine, human corneal stromal stem cells (CSSCs) could serve as a powerful tool for drug discovery and development. Variations from different donors, their isolation method, and their limited life span in culture hinder the utility of primary human CSSCs. To address these limitations, this study aims to establish and characterize immortalized CSSC lines (imCSSC) generated from primary human CSSCs. Primary CSSCs (pCSSC), isolated from human adult corneoscleral tissue, were transduced with ectopic expression of hTERT, c-MYC, or the large T antigen of the Simian virus 40 (SV40T) to generate imCSSC. Cellular morphology, proliferation capacity, and expression of CSSCs specific surface markers were investigated in all cell lines, including TNFAIP6 gene expression levels in vitro, a known biomarker of in vivo anti-inflammatory efficacy. SV40T-overexpressing imCSSC successfully extended the lifespan of pCSSC while retaining a similar morphology, proliferative capacity, multilineage differentiation potential, and anti-inflammatory properties. The current study serves as a proof-of-concept that immortalization of CSSCs could enable a large-scale source of CSSC for use in regenerative medicine.

CXC- receptor 2 promotes extracellular matrix production and attenuates migration in peripapillary human scleral fibroblasts under mechanical strain.

As the main loading-bearing tissue of eye, sclera exerts an important role in the pathophysiology of glaucoma. Intraocular pressure (IOP) generates mechanical strain on sclera. Recent studies have demonstrated that sclera, especially the peripapillary sclera, undergoes complicated remodelling under the mechanical strain. However, the mechanisms of the hypertensive scleral remodelling in human eyes remained uncertain. In this study, peripapillary human scleral fibroblasts (ppHSFs) were applied cyclic mechanical strain by Flexcell-5000™ tension system. We found that CXC- ligands and CXCR2 were differentially expressed after strain. Increased cell proliferation and inhibited cell motility were observed when CXCR2 was upregulated under the strain, whereas cell proliferation and motility did not have a significant change when CXCR2 was knocked down. CXCR2 could facilitate cell proliferation ability, modulate the mRNA and protein expressions of type I collagen and matrix metalloproteinase 2 via JAK1/2-STAT3 signalling pathway. In addition, CXCR2 might inhibit cell migration via FAK/MLC2 pathway. Taken together, CXCR2 regulated protein production and affected cell behaviours of ppHSFs. It might be a potential therapeutic target for the hypertensive scleral remodelling.