The viral antigen (Ag)-specific CD8 cytotoxic T lymphocytes (CTLs) derived from pluripotent stem cells (PSCs), i.e., PSC-CTLs, have the ability to suppress hepatitis B virus (HBV) infection. After adoptive transfer, PSC-CTLs can infiltrate into the liver to suppress HBV replication. Nevertheless, the mechanisms by which the viral Ag-specific PSC-CTLs provoke the antiviral response remain to be fully elucidated. In this study, we generated the functional HBV surface Ag-specific CTLs from the induced PSC (iPSCs), i.e., iPSC-CTLs, and investigated the underlying mechanisms of the CTL-mediated antiviral replication in a murine model. We show that adoptive transfer of HBV surface Ag-specific iPSC-CTLs greatly suppressed HBV replication and prevented HBV surface Ag expression. We further demonstrate that the adoptive transfer significantly increased T cell accumulation and production of antiviral cytokines. These results indicate that stem cell-derived viral Ag-specific CTLs can robustly accumulate in the liver and suppress HBV replication through producing antiviral cytokines.

PURPOSE: To quantify the resident learning curve for cataract surgery using operative time as an indicator of surgical competency, to identify the case threshold at which marginal additional educational benefit became equivocal, and to characterize heterogeneity in residents' pathways to surgical competency. SETTING: Academic medical center. DESIGN: Large-scale retrospective consecutive case series. METHODS: All cataract surgery cases performed by resident physicians as primary surgeon at Massachusetts Eye and Ear from July 1, 2010, through June 30, 2015, were reviewed. Data were abstracted from Accreditation Council for Graduate Medical Education case logs and operative time measurements. A linear mixed-methods analysis was conducted to model changes in residents' cataract surgery operative times as a function of sequential case number, with resident identity included as a random effect in the model to normalize between-resident variability. RESULTS: A total of 2096 cases were analyzed. A marked progressive decrease in operative time was noted for resident cases 1 to 39 (mean change -0.17 minutes per additional case, 95% CI, -0.21 to -0.12; P < .001). A modest, steady reduction in operative time was subsequently noted for case numbers 40 to 149 (mean change -0.05 minutes per additional case, 95% CI, -0.07 to -0.04; P < .001). No statistically significant improvement was found in operative times beyond the 150th case. CONCLUSIONS: Residents derived educational benefit from performing a greater number of cataract procedures than current minimum requirements. However, cases far in excess of this threshold might have diminishing educational return in residency. Educational resources currently used for these cases might be more appropriately devoted to other training priorities.

Integrins mediate adhesion of cells to substrates and maintain tissue integrity by facilitating mechanotransduction between cells, the extracellular matrix, and gene expression in the nucleus. Changes in integrin expression in corneal epithelial cells and corneal endothelial cells impacts their adhesion to the epithelial basement membrane (EpBM) and Descemet's membrane, respectively. Integrins also play roles in assembly of basement membranes by both activating TGFβ1 and other growth factors. Over the past two decades, this knowledge has been translated into methods to grow corneal epithelial and endothelial cells in vitro for transplantation in the clinic thereby transforming clinical practice and quality of life for patients. Current knowledge on the expression and function of the integrins that mediate adhesion to the basement membrane expressed by corneal epithelial and endothelial cells in health and disease is summarized. This is the first review to discuss similarities and differences in the integrins expressed by both cell types.

PURPOSE: Angle surgery is the gold standard for the management of many types of childhood glaucoma, yet glaucoma drainage devices (GDD) are effective tools for refractory advanced cases or secondary childhood glaucomas. The purpose of this article is to review recently published literature focused on the use of GDDs for pediatric glaucoma, including GDD general principles and surgical outcomes. METHODS: Literature review of various electronic databases was performed. RESULTS: 71 papers were reviewed for outcomes of GDD in childhood glaucomas. Success rates were usually defined by intraocular pressure (IOP) of 5-22 mmHg, with or without medications. Success rates were typically higher for non-valved GDDs but varied by length of follow-up. Non-valved GDDs afford lower and longer-lasting IOP control in pediatric eyes than valved GDD, however, no randomized controlled trials exist in childhood glaucoma. CONCLUSION: Various designs of GDDs are available for management of childhood glaucoma with good short-term success rates; individual patient factors should be taken into consideration when selecting a specific device.

PURPOSE: To report the clinical findings, anatomical features, and treatment outcomes in subjects with ocular tuberculosis (OTB) at 24 months in the Collaborative Ocular Tuberculosis Study (COTS)-1. METHODS: Of the 945 subjects included in COTS-1, those who completed a 24-month follow-up after completion of treatment were included. The main outcome measure was a number of patients with treatment failure (TF). RESULTS: 228 subjects (120 males; mean age of 42.82 ± 14.73 years) were included. Most common phenotype of uveitis was posterior ( = 81; 35.53%), and panuveitis ( = 76; 33.33%). Fifty-two patients (22.81%) had TF. On univariable analysis, odds of high TF was observed with bilaterality (OR: 3.46, = .003), vitreous haze (OR: 2.14, = .018), and use of immunosuppressive therapies (OR: 5.45, = .003). However, only bilaterality was significant in the multiple regression model (OR: 2.84; = .02). CONCLUSIONS: Majority of subjects (>75%) achieved cure in the COTS-1 at 24-month follow-up. The concept of "cure" may be a valuable clinical endpoint in trials for OTB.

The nuclei of cone photoreceptors are located on the apical side of the outer nuclear layer (ONL) in vertebrate retinas. However, the functional role of this evolutionarily conserved localization of cone nuclei is unknown. We previously showed that Linkers of the Nucleoskeleton to the Cytoskeleton (LINC complexes) are essential for the apical migration of cone nuclei during development. Here, we developed an efficient genetic strategy to disrupt cone LINC complexes in mice. Experiments with animals from both sexes revealed that disrupting cone LINC complexes resulted in mislocalization of cone nuclei to the basal side of ONL in mouse retina. This, in turn, disrupted cone pedicle morphology, and appeared to reduce the efficiency of synaptic transmission from cones to bipolar cells. Although we did not observe other developmental or phototransduction defects in cones with mislocalized nuclei, their dark adaptation was impaired, consistent with a deficiency in chromophore recycling. These findings demonstrate that the apical localization of cone nuclei in the ONL is required for the timely dark adaptation and efficient synaptic transmission in cone photoreceptors.

Platelet-derived growth factor (PDGF) is associated with clinical proliferative vitreoretinopathy (PVR), which is characterized by formation of sub- or epi-retinal membranes that consist of cells including retinal pigment epithelial （RPE） cells and extracellular matrix. RPE cells play an important role in PVR pathogenesis. Previous findings indicated that PDGF receptor (PDGFR)α was essential in experimental PVR induced by fibroblasts. In RPE cells derived from epiretinal membranes from patients with PVR (RPEMs)， Akt was activated by PDGF-B but not PDGF-A, which suggested that PDGFRβ was the predominant PDGFR isoform expressed in RPEMs. Indeed, CRISPR/Cas9-mediated depletion of PDGFRβ in RPEMs attenuated patient vitreous-induced Akt activation and cellular responses intrinsic to PVR including cell proliferation, migration, and contraction. We conclude that PDGFRβ appears to be the PVR relevant PDGFR isoform in RPEMs.