Wiseeaton9288

Purpose Herpes simplex virus type I (HSV-1) infection of corneal epithelial cells activates ataxia telangiectasia mutated (ATM), an apical kinase in the host DNA damage response pathway, whose activity is necessary for the progression of lytic HSV-1 infection. The purpose of this study is to investigate the mechanism of ATM activation by HSV-1 in the corneal epithelium, as well as its functional significance. Methods Mechanistic studies were performed in cultured human corneal epithelial cell lines (hTCEpi, HCE), as well as in esophageal (EPC2) and oral (OKF6) cell lines. Transfection-based experiments were performed in HEK293 cells. HSV-1 infection was carried out using the wild-type KOS strain, various mutant strains (tsB7, d120, 7134, i13, n208), and bacterial artificial chromosomes (fHSVΔpac, pM24). Inhibitors of ATM (KU-55933), protein synthesis (cycloheximide), and viral DNA replication (phosphonoacetic acid) were used. Outcomes of infection were assayed using Western blotting, qRT-PCR, immunofluorescence, and comet assay. Results This study demonstrates that HSV-1-mediated ATM activation in corneal epithelial cells relies on the viral immediate early gene product ICP4 and requires the presence of the viral genome in the host nucleus. We show that ATM activation is independent of viral genome replication, the ICP0 protein, and the presence of DNA lesions. Interestingly, ATM activity appears to be necessary at the onset of infection, but dispensable at the later stages. Conclusions This study expands our understanding of HSV-1 virus-host interactions in the corneal epithelium and identifies potential areas of future investigation and therapeutic intervention in herpes keratitis.Purpose The purpose of this study was to investigate changes in lamina cribrosa (LC) depth after trabeculectomy in myopic eyes using enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD-OCT). Methods Serial horizontal B-scans of the optic nerve head of 41 myopic eyes with primary open-angle glaucoma (POAG) were obtained before and 3 months after trabeculectomy using EDI SD-OCT. JAK drugs LC depth, defined as the distance from the opening plane of Bruch's membrane to the level of the anterior LC surface, was measured before and 3 months after trabeculectomy at 7 locations spaced equidistantly across the vertical optic disc diameter on B-scan images. The mean of the measurements at these seven planes was defined as the average LC depth. Factors associated with changes in LC depth were identified by linear regression. Results Intraocular pressure (IOP) decreased from 26.3 ± 9.3 millimeters of mercury (mm Hg) preoperatively to 10.6 ± 3.5 mm Hg 3 months after trabeculectomy. LC depth was significantly lower 3 months after trabeculectomy than preoperatively (P less then 0.001, all planes). The magnitude of LC depth reduction was significantly associated with younger age, higher preoperative LC depth, and greater magnitude of IOP reduction (all P ≤ 0.016). Conclusions LC depth reduction was observed after trabeculectomy in myopic eyes. The degree of LC depth reduction was not related to the degree of myopia.Purpose Corneal ulcers are a common eye inflammatory disease that can cause visual impairment or even blindness if not treated promptly. Ocular trauma is a major risk factor for corneal ulcers, and corneal trauma in agricultural work can rapidly progress to corneal ulcers. This study aims to evaluate the changes in the ocular surface (OS) microbiome of patients with traumatic corneal ulcer (TCU). Methods Among 20 healthy control (HC) subjects and 22 patients with TCU, 42 eyes were examined to investigate the OS microbial flora using metagenomic shotgun sequencing. Results At the taxonomic composition level, our findings showed that dysbiosis (alterations in richness and community structure) occurs in the OS microbiome of patients with TCU. Notably, Pseudomonas was present at a greater than 30% relative abundance in all individuals in the TCU group. At the species level, the abundance of Pseudomonas fluorescens and Pseudomonas aeruginosa was significantly elevated in the TCU group compared to the HC group. At the functional level, we identified significant differences in the HC and TCU groups. We observed that inflammation-related pathways involved in bacterial chemotaxis, flagellar assembly, and biofilm formation were significantly more abundant in the TCU group. Besides, the pathways related to biosynthesis, degradation, and metabolism were also increased significantly in the TCU group. Conclusions These findings indicate an altered OS microbiome in the affected eyes of patients with TCU. Further research is needed to determine whether these alterations contribute to the pathogenesis of TCU or impact disease progression.The interleukin (IL)-1 system plays a major role in immune responses and inflammation. The IL-1 system components include IL-1α, IL-1β, IL-1 receptor type 1 and IL-1 receptor type 2 (decoy receptor), IL-1 receptor accessory protein (IL-1RAcP), and IL-1 receptor antagonist (IL-1Ra). These components have been shown to play a role in pregnancy, specifically in embryo-maternal communication for implantation, placenta development, and protection against infections. As gestation advances, maternal tissues experience increasing fetal demand and physical stress and IL-1β is induced. Dependent on the levels of IL-1Ra, which regulates IL-1β activity, a pro-inflammatory response may or may not occur. If there is an inflammatory response, prostaglandins are synthesized which may lead to myometrial contractions and the initiation of labor. Many studies have examined the role of the IL-1 system in pregnancy by independently measuring plasma, cervical and amniotic fluid IL-1β or IL-1Ra levels. Other studies have tested for polymorphisms in IL-1β and IL-1Ra genes in women experiencing pregnancy complications such as early pregnancy loss, in vitro fertilization (IVF) failure, pre-eclampsia and preterm delivery. Data from those studies suggest a definite role for the IL-1 system in successful pregnancy outcomes. However, as anticipated, the results varied among different experimental models, ethnicities, and disease states. Here, we review the current literature and propose that measurement of IL-1Ra in relation to IL-1 may be useful in predicting the risk of poor pregnancy outcomes.