Psoriasis is an inflammatory skin disease with strong neutrophil (PMN) infiltration and high levels of the antimicrobial peptide, LL37. LL37 in complex with DNA and RNA is thought to initiate disease exacerbation via plasmacytoid dendritic cells. However, the source of nucleic acids supposed to start this initial inflammatory event remains unknown. We show here that primary murine and human PMNs mount a fulminant and self-propagating neutrophil extracellular trap (NET) and cytokine response, but independently of the canonical NET component, DNA. Unexpectedly, RNA, which is abundant in NETs and psoriatic but not healthy skin, in complex with LL37 triggered TLR8/TLR13-mediated cytokine and NET release by PMNs in vitro and in vivo. Transfer of NETs to naive human PMNs prompts additional NET release, promoting further inflammation. Our study thus uncovers a self-propagating vicious cycle contributing to chronic inflammation in psoriasis, and NET-associated RNA (naRNA) as a physiologically relevant NET component.

Post-chiasmal visual pathway lesions and glaucomatous optic neuropathy cause binocular visual field defects (VFDs) that may critically interfere with quality of life and driving licensure. The aims of this study were (i) to assess the on-road driving performance of patients suffering from binocular visual field loss using a dual-brake vehicle, and (ii) to investigate the related compensatory mechanisms. A driving instructor, blinded to the participants' diagnosis, rated the driving performance (passed/failed) of ten patients with homonymous visual field defects (HP), including four patients with right (HR) and six patients with left homonymous visual field defects (HL), ten glaucoma patients (GP), and twenty age and gender-related ophthalmologically healthy control subjects (C) during a 40-minute driving task on a pre-specified public on-road parcours. In order to investigate the subjects' visual exploration ability, eye movements were recorded by means of a mobile eye tracker. Two additional cameras were used to monitor the driving scene and record head and shoulder movements. Thus this study is novel as a quantitative assessment of eye movements and an additional evaluation of head and shoulder was performed. Six out of ten HP and four out of ten GP were rated as fit to drive by the driving instructor, despite their binocular visual field loss. Three out of 20 control subjects failed the on-road assessment. The extent of the visual field defect was of minor importance with regard to the driving performance. The site of the homonymous visual field defect (HVFD) critically interfered with the driving ability: all failed HP subjects suffered from left homonymous visual field loss (HL) due to right hemispheric lesions. Patients who failed the driving assessment had mainly difficulties with lane keeping and gap judgment ability. Patients who passed the test displayed different exploration patterns than those who failed. Patients who passed focused longer on the central area of the visual field than patients who failed the test. In addition, patients who passed the test performed more glances towards the area of their visual field defect. In conclusion, our findings support the hypothesis that the extent of visual field per se cannot predict driving fitness, because some patients with HVFDs and advanced glaucoma can compensate for their deficit by effective visual scanning. Head movements appeared to be superior to eye and shoulder movements in predicting the outcome of the driving test under the present study scenario.

Advanced glaucomatous visual field loss may critically interfere with quality of life. The purpose of this study was to (i) assess the impact of binocular glaucomatous visual field loss on a supermarket search task as an example of everyday living activities, (ii) to identify factors influencing the performance, and (iii) to investigate the related compensatory mechanisms. Ten patients with binocular glaucoma (GP), and ten healthy-sighted control subjects (GC) were asked to collect twenty different products chosen randomly in two supermarket racks as quickly as possible. The task performance was rated as “passed” or “failed” with regard to the time per correctly collected item. Based on the performance of control subjects, the threshold value for failing the task was defined as μ+3σ (in seconds per correctly collected item). Eye movements were recorded by means of a mobile eye tracker. Eight out of ten patients with glaucoma and all control subjects passed the task. Patients who failed the task needed significantly longer time (111.47 s ±12.12 s) to complete the task than patients who passed (64.45 s ±13.36 s, t-test, p<0.001). Furthermore, patients who passed the task showed a significantly higher number of glances towards the visual field defect (VFD) area than patients who failed (t-test, p<0.05). According to these results, glaucoma patients with defects in the binocular visual field display on average longer search times in a naturalistic supermarket task. However, a considerable number of patients, who compensate by frequent glancing towards the VFD, showed successful task performance. Therefore, systematic exploration of the VFD area seems to be a “time-effective” compensatory mechanism during the present supermarket task.