This study provides the first evidence that homocysteine-induced ganglion cell loss involves the dysregulation of mitochondrial dynamics, both in vivo and in vitro. The present data suggest increased mitochondrial fission as a novel mechanism of homocysteine toxicity to neurons. Of particular relevance are glaucoma and Alzheimer's disease, neurodegenerative diseases that are associated with hyperhomocysteinemia and, more recently, have implicated increased mitochondrial fission in their pathogeneses.

The high affinity Sigma Receptor 1 (σR1) ligand (+)-pentazocine ((+)-PTZ) affords profound retinal neuroprotection in vitro and in vivo by a yet-unknown mechanism. A common feature of retinal disease is Müller cell reactive gliosis, which includes cytokine release. Here we investigated whether LPS stimulates cytokine release by primary mouse Müller cells and whether (+)-PTZ alters release. Using a highly sensitive inflammatory antibody array we observed significant release of macrophage inflammatory proteins (MIP1γ, MIP2, MIP3α) and interleukin-12 (IL12 (p40/p70)) in LPS-treated cells compared to controls, and a significant decrease in secretion upon (+)-PTZ treatment. Müller cells from σR1 knockout mice demonstrated increased MIP1γ, MIP2, MIP3α and IL12 (p40/p70) secretion when exposed to LPS compared to LPS-stimulated WT cells. We investigated whether cytokine secretion was accompanied by cytosolic-to-nuclear NFκB translocation and whether endothelial cell adhesion/migration was altered by released cytokines. Cells exposed to LPS demonstrated increased NFκB nuclear location, which was reduced significantly in (+)-PTZ-treated cells. Media conditioned by LPS-stimulated-Müller cells induced leukocyte-endothelial cell adhesion and endothelial cell migration, which was attenuated by (+)-PTZ treatment. The findings suggest that release of certain inflammatory cytokines by Müller cells can be attenuated by σR1 ligands providing insights into the retinal neuroprotective role of this receptor.

No abstract

Nanoscale characterization techniques are fundamental to continue increasing the performance and miniaturization of consumer electronics. Among all the available techniques, Kelvin-probe force microscopy (KPFM) provides nanoscale maps of the local work function, a paramount property related to many chemical and physical surface phenomena. For this reason, this technique has being extremely employed in the semiconductor industry, and now is becoming more and more important in the growing field of 2D materials, providing information about the electronic properties, the number of layers, and even the morphology of the samples. However, although all the collective efforts from the community, proper calibration of the technique to obtain reliable and consistent work-function values is still challenging. Here we show a calibration method that improves on current procedures by reducing the uncertainty. In particular, it allows grading probes more easily, thus being a tool to calibrate and to judge calibration in itself. The calibration method is applied to optimize Pt-coated probes, which are then used to characterize the work function of a 2D material, i.e. graphite flakes. The results demonstrate that the metallic probes are stable over time and exposure to high humidity levels, and that the calibration allows comparing measurements taken with several different probes on different samples, thus completely fulfilling the requirement of a good calibration method.