Size and surface modification of silica nanoparticles affect the severity of lung toxicity by modulating endosomal ROS generation in macrophages.

BACKGROUND: As the application of silica nanomaterials continues to expand, increasing chances of its exposure to the human body and potential harm are anticipated. Although the toxicity of silica nanomaterials is assumed to be affected by their physio-chemical properties, including size and surface functionalization, its molecular mechanisms remain unclear. We hypothesized that analysis of intracellular localization of the particles and subsequent intracellular signaling could reveal a novel determinant of inflammatory response against silica particles with different physico-chemical properties. RESULTS: We employed a murine intratracheal instillation model of amorphous silica nanoparticles (NPs) exposure to compare their in vivo toxicities in the respiratory system. Pristine silica-NPs of 50 nm diameters (50 nm-plain) induced airway-centered lung injury with marked neutrophilic infiltration. By contrast, instillation of pristine silica particles of a larger diameter (3 µm; 3 µm-plain) significantly reduced the severity of lung injury and neutrophilic infiltration, possibly through attenuated induction of neutrophil chemotactic chemokines including MIP2. Ex vivo analysis of alveolar macrophages as well as in vitro assessment using RAW264.7 cells revealed a remarkably lower cellular uptake of 3 µm-plain particles compared with 50 nm-plain, which is assumed to be the underlying mechanism of attenuated immune response. The severity of lung injury and neutrophilic infiltration was also significantly reduced after intratracheal instillation of silica NPs with an amine surface modification (50 nm-NH2) when compared with 50 nm-plain. Despite unchanged efficacy in cellular uptake, treatment with 50 nm-NH2 induced a significantly attenuated immune response in RAW264.7 cells. Assessment of intracellular redox signaling revealed increased reactive oxygen species (ROS) in endosomal compartments of RAW264.7 cells treated with 50 nm-plain when compared with vehicle-treated control. In contrast, augmentation of endosomal ROS signals in cells treated with 50 nm-NH2 was significantly lower. Moreover, selective inhibition of NADPH oxidase 2 (NOX2) was sufficient to inhibit endosomal ROS bursts and induction of chemokine expressions in cells treated with silica NPs, suggesting the central role of endosomal ROS generated by NOX2 in the regulation of the inflammatory response in macrophages that endocytosed silica NPs. CONCLUSIONS: Our murine model suggested that the pulmonary toxicity of silica NPs depended on their physico-chemical properties through distinct mechanisms. Cellular uptake of larger particles by macrophages decreased, while surface amine modification modulated endosomal ROS signaling via NOX2, both of which are assumed to be involved in mitigating immune response in macrophages and resulting lung injury.

Primary rhegmatogenous retinal detachment: evaluation of a minimally restricted face-down positioning after pars plana vitrectomy and gas tamponade.

AIM: To evaluate the safety and efficacy of a minimally restricted face-down postoperative positioning following pars plana vitrectomy (PPV) with gas tamponade for primary rhegmatogenous retinal detachment (RRD). METHODS: Patients with primary RRD treated with PPV and gas tamponade and followed up for at least 6mo were selected for the study. All phakic eyes underwent simultaneous cataract surgery. The patients were required to be in a postoperative position that prevented downward flow of retinal tears. Patients with macular detachment were positioned face-down for only a couple of hours. The patients were assessed for preoperative and postoperative best-corrected visual acuity (BCVA), anatomical retinal reattachment rate, and postoperative complications. RESULTS: In total, 40 eyes of 39 patients with primary RRD were included in the study. A single tear was present in 30 eyes (75.0%), multiple retinal tears were present in nine eyes (22.5%), and oral dialysis was present in one eye (2.5%). The anatomical success rate was 90.0% (36 cases) after the primary surgery, and the final anatomical success rate was 100%. The BCVA improved significantly (P<0.001) from 0.75 logarithm angle of resolution (logMAR) preoperatively to 0.12 logMAR at the final visit. Postoperative complications included intraocular pressure elevation (≥25 mm Hg) in 11 patients (27.5%), fibrin formation in two patients (5.0%), pupillary capture of the intraocular lens in two patients (5.0%), and posterior synechia in one patient (2.5%). CONCLUSION: A minimally restricted face-down and flexible postoperative positioning after PPV and gas tamponade for primary RRD is effective and safe.

Optimal Display Positions for Heads-Up Surgery to Minimize Crosstalk.

Purpose: To determine optimal display positions during heads-up surgery (HUS) to minimize crosstalk. Methods: Three three-dimensional (3D) displays were analyzed to evaluate the relationship between display position and amount of crosstalk. First, the 3D displays were calibrated to show a completely white image in the right eye and completely black image in the left eye. Images were captured through the polarized filter, which corresponded to the left-eye image. The amount of crosstalk in the left eye was measured as white areas on the black background that originated from the right-eye image. The amount of crosstalk was measured at different display distances and heights to estimate the non-crosstalk display positions for each display. Results: Varying amounts of crosstalk (0%-70.3%) were observed for different display distances and heights. The crosstalk almost always started from the corner of the display, although the starting area varied according to the type of display. The minimum distance of non-crosstalk position was 1.26 meters away from display 1, 1.24 meters away from display 2, and 1.8 meters away from display 3. With regard to display height, the optimal center-of-display heights for displays 1, 2, and 3 were 72 mm below, 18 mm above, and 101 mm above eye level, respectively. Conclusions: The amount of crosstalk differed according to display positions and displays. Translational Relevance: The optimal HUS display settings differ among displays; therefore, each surgeon should carefully evaluate individual display characteristics before using HUS in practice.