PAX6-positive microglia evolve locally in hiPSC-derived ocular organoids

Microglia are the resident immune cells of the central nervous system (CNS). They govern the immunogenicity of the retina, which is considered to be part of the CNS; however, it is not known how microglia develop in the eye. Here, we studied human-induced pluripotent stem cells (hiPSCs) that had been expanded into a self-formed ectodermal autonomous multi-zone (SEAM) of cells that partially mimics human eye development. Our results indicated that microglia-like cells, which have characteristics of yolk-sac-like linage cells, naturally develop in 2D eye-like SEAM organoids, which lack any vascular components. These cells are unique in that they are paired box protein 6 (PAX6)-positive, yet they possess some characteristics of mesoderm. Collectively, the data support the notion of the existence of an isolated, locally developing immune system in the eye, which is independent of the body’s vasculature and general immune system

Vitrectomy without prone positioning for rhegmatogenous retinal detachments in eyes with inferior retinal breaks

<div><p>Purpose</p><p>To compare the anatomic and functional outcomes of pars plana vitrectomy (PPV) for treating rhegmatogenous retinal detachments (RRDs) between two groups with and without postoperative prone positioning.</p><p>Methods</p><p>This retrospective cohort study included 142 eyes of 142 patients with a primary RRD. All patients underwent PPV with 20% sulfur hexafluoride gas tamponade and were divided into two groups: the groups that did and did not maintain a prone position postoperatively. All patients were followed for more than 3 months. The main outcome measures were the best-corrected visual acuity (BCVA), retinal reattachment rate, and postoperative complications.</p><p>Results</p><p>Sixty-five eyes were included in the prone position group and 77 eyes in the group without prone positioning; the respective initial reattachment rates were 83.1% and 96.1%, a difference that reach significance (p = 0.011). In the eyes with inferior breaks, the initial reattachment rate was 94.7% (18 eyes) without prone positioning, which was significantly (p = 0.036) better than the 60% (6 eyes) initial reattachment rate in the group with prone positioning. In the eyes without inferior breaks, there was no significant difference in the initial reattachment rates between the two groups. The BCVAs at the 3-month postoperative visit did not differ significantly between the two groups. An epiretinal membrane (ERM) was observed postoperatively in 10 (13.0%) eyes in the group without prone positioning; no ERMs were seen postoperatively in eyes in which the internal limiting membrane (ILM) was peeled during PPV.</p><p>Conclusions</p><p>PPV without postoperative prone positioning is associated with a higher reattachment rate in eyes with a RRD, especially those with inferior retinal breaks. PPV with postoperative supine and lateral positioning might be beneficial to manage RRDs associated with inferior retinal breaks if ILM peeling is performed intraoperatively.</p></div

Mechanism of Action of T-705 against Influenza Virus

T-705, a substituted pyrazine compound, has been found to exhibit potent anti-influenza virus activity in vitro and in vivo. In a time-of-addition study, it was indicated that T-705 targeted an early to middle stage of the viral replication cycle but had no effect on the adsorption or release stage. The anti-influenza virus activity of T-705 was attenuated by addition of purines and purine nucleosides, including adenosine, guanosine, inosine, and hypoxanthine, whereas pyrimidines did not affect its activity. T-705-4-ribofuranosyl-5′-triphosphate (T-705RTP) and T-705-4-ribofuranosyl-5′-monophosphate (T-705RMP) were detected in MDCK cells treated with T-705. T-705RTP inhibited influenza virus RNA polymerase activity in a dose-dependent and a GTP-competitive manner. Unlike ribavirin, T-705 did not have an influence on cellular DNA or RNA synthesis. Inhibition of cellular IMP dehydrogenase by T-705RMP was about 150-fold weaker than that by ribavirin monophosphate, indicating the specificity of the anti-influenza virus activity and lower level of cytotoxicity of T-705. These results suggest that T-705RTP, which is generated in infected cells, may function as a specific inhibitor of influenza virus RNA polymerase and contributes to the selective anti-influenza virus activity of T-705

Risk factors for recurrence of RD in the subgroup of inferior breaks.

<p>Risk factors for recurrence of RD in the subgroup of inferior breaks.</p

Postoperative outcome measures after vitrectomy with prone positioning versus without prone positioning.

<p>Postoperative outcome measures after vitrectomy with prone positioning versus without prone positioning.</p