Evaluation of different OCT systems in quantitative imaging of human Schlemm's canal.

We examined the performance of human Schlemm's canal (SC) imaging using different OCT devices: CIRRUS 5000 (840 nm, spectral-domain (SD)-OCT), PLEX Elite 9000 (1060 nm, swept-source (SS)-OCT) and CASIA SS-1000 (1310 nm, SS-OCT), and analyzed potential impact factors on visualization and the quantitative assessment of SC morphology in a pilot study. Ten healthy subjects were imaged using three OCT devices by a single experienced operator on the same day. Each eye underwent two cubic scans by each device, one on nasal and the other on temporal quadrant. The B-scan showing the largest SC was manually selected for processing. Four quantitative metrics, including one morphological metric as cross-sectional area (CSA), and three performance metrics as contrast, continuity, and coverage, were derived from the datasets. Repeated-measures ANOVA was used to investigate the difference between these parameters from the three devices (P < 0.05). We found the CSA measured from CIRRUS was significantly larger than PLEX, followed by CASIA. The contrast was highest in CIRRUS, followed by PLEX and CASIA. The coverage was also higher in CIRRUS as compared to PLEX and CASIA. No significant difference was seen in the continuity from the three devices. In summary, we showed the measurements from the three devices were not interchangeable.

STING-dependent cytosolic DNA sensor pathways regulate NKG2D ligand expression.

The DNA damage response (DDR) upregulates the expression of NKG2D ligands (NKG2DLs).1,2 We have recently reported that the DDR also induces the presence of cytosolic DNA in B-cell lymphoma cells, which leads to the activation of STING-dependent cytosolic DNA sensor pathways and the expression of RAE-1 ligands for NKG2D.3.

RAE1 ligands for the NKG2D receptor are regulated by STING-dependent DNA sensor pathways in lymphoma.

The immunoreceptor NKG2D originally identified in natural killer (NK) cells recognizes ligands that are upregulated on tumor cells. Expression of NKG2D ligands (NKG2DL) is induced by the DNA damage response (DDR), which is often activated constitutively in cancer cells, revealing them to NK cells as a mechanism of immunosurveillance. Here, we report that the induction of retinoic acid early transcript 1 (RAE1) ligands for NKG2D by the DDR relies on a STING-dependent DNA sensor pathway involving the effector molecules TBK1 and IRF3. Cytosolic DNA was detected in lymphoma cell lines that express RAE1 and its occurrence required activation of the DDR. Transfection of DNA into ligand-negative cells was sufficient to induce RAE1 expression. Irf3(+/-);Eµ-Myc mice expressed lower levels of RAE1 on tumor cells and showed a reduced survival rate compared with Irf3(+/+);Eµ-Myc mice. Taken together, our results suggest that genomic damage in tumor cells leads to activation of STING-dependent DNA sensor pathways, thereby activating RAE1 and enabling tumor immunosurveillance.