Increased oxidative stress and mitochondrial damage are observed in protein aggregation diseases, such as age-related macular degeneration (AMD). We have recently reported elevated levels of oxidative stress markers, damaged mitochondria, accumulating lysosomal lipofuscin and extracellular drusen-like structures in the retinal pigment epithelial cells (RPE) of the dry AMD-resembling NFE2L2/PGC1α double knockout (dKO) mouse model. Here, we provide evidence of a disturbance in the autolysosomal machinery handling mitochondrial clearance in the RPE cells of one-year-old NFE2L2/PGC1α-deficient mice. Confocal immunohistochemical analysis revealed an upregulation of autophagosome marker microtubule-associated proteins 1A/1B light chain 3B (LC3B) as well as numerous mitophagy markers, such as PTE-induced putative kinase 1 (PINK1) and E3 ubiquitin ligase (PARKIN) together with damaged mitochondria. However, we detected no evidence of increased autolysosome formation in transmission electron micrographs or of colocalization of lysosomal marker LAMP2 (lysosome-associated membrane protein 2) and the mitochondrial marker ATP synthase β in confocal micrographs. Interestingly, we observed an upregulation of late autolysosomal fusion Ras-related protein (Rab7) in the perinuclear space of RPE cells together with autofluorescence aggregates. Our results reveal that there is at least a relative decrease of mitophagy in the RPE cells of NFE2L2/PGC1α dKO mice. This further supports the hypothesis that mitophagy is a putative therapy target in AMD-like pathology.

Idiopathic intracranial hypertension (IIH) is aetiologically unknown disorder that associates with endocrinological disturbances, including dysfunction of hypothalamic-pituitary-adrenal-axis. Neuroendocrinological dysfunctions have also been characterized in psychiatric disorders, and therefore we investigated the presence of psychiatric disorders of patients with IIH in a well-defined cohort. A total of 51 patients with IIH were included. Patient demographics, symptoms, imaging data, ophthalmological and clinical findings were collected. At the time of diagnosis the mean age was 32.5years (SD 10.7), the body mass index was 37.1 kg/m2 (SD 7.4), and the opening pressure 29.1 mmHg (SD 6.2). A total of 88.2% of patients were female and 45.1% were diagnosed with a psychiatric co-morbidity prior to IIH diagnosis. The mean follow-up time was 4.4 years (SD 5.4). The overall treatment outcome was significantly poorer on a group of patients with psychiatric diagnosis when compared to individuals without such history (p = 0.001), but there were no differences in the resolution of papilledema (p = 0.405). Patients with IIH and psychiatric disorders had more often empty sella on their imaging at diagnosis when compared to patients without psychiatric co-morbidity (p = 0.044). Psychiatric disorders are highly prevalent in patients with IIH and associate with worse subjective outcomes. These findings advocate for monitoring the mental health of patients with IIH and warrant further multidisciplinary research to understand the potentially underlying psychosocial and neuroendocrinological mechanisms.

Objectives: To evaluate the effectiveness of safety guidelines in the workplace, the authors analyzed the work-related exposure to SARS-CoV-2 and the source of COVID‑19 infections among healthcare workers (HCWs), together with the use of personal protective equipment (PPE). Material and...

The aim of the study was to investigate the influence of complement component C3 global depletion on the biological structure and function of the aged retina. In vivo morphology (OCT), electrophysiological function (ERG), and the expression of selected oxidative stress‐, apoptosis‐, and autophagy‐related proteins were assessed in retinas of 12‐month‐old C3‐deficient and WT mice. Moreover, global gene expression in retinas was analyzed by RNA arrays. We found that the absence of active C3 was associated with (1) alleviation of the age‐dependent decrease in retinal thickness and gradual deterioration of retinal bioelectrical function, (2) significantly higher levels of antioxidant enzymes (catalase and glutathione reductase) and the antiapoptotic survivin and Mcl‐1/Bak dimer, (3) lower expression of the cellular oxidative stress marker—4HNE—and decreased activity of proapoptotic caspase‐3, (4) ameliorated retinal autophagic activity with localization of ubiquitinated protein conjugates commonly along the retinal pigment epithelium (RPE) layer, and (5) significantly increased expression of several gene sets associated with maintenance of the physiological functions of the neural retina. Our findings shed light on mechanisms of age‐related retinal alterations by identifying C3 as a potential therapeutic target for retinal aging.

Objective: To analyse the work-related exposure to SARS-CoV-2 and trace the source of COVID-19 infections in tertiary hospitals’ healthcare workers in light of the used PPE and their ability to maintain social distances and follow governmental restrictions. Design: Cross-sectional study Setting: Tertiary hospitals in Uusimaa region, Finland Participants: Of 1072 enrolled, 866 HCWs (588 nurses, 170 doctors and 108 laboratory and medical imaging nurses) from the Helsinki University Hospital completed the questionnaire by July 15 ^th , 2020. The average age of participants was 42.4 years and 772 (89.0%) were women. The participants answered a detailed questionnaire of their PPE usage, ability to follow safety restrictions, exposure to COVID-19, the source of potential COVID-19 infection and both mental and physical symptoms during the first wave of COVID-19 in Finland. Main outcome measures: All participants with COVID-19 symptoms were tested with either RT-PCR or antibody tests. The infections were traced and categorised based on the location and source of infection. The possibility to maintain social distance and PPE usage during exposure were analyzed. Results: Of the HCWs that participated, 41 (4.7%) tested positive for SARS-CoV-2, marking a substantially higher infection rate than that of the general population (0.3%); 22 (53.6%) of infections were confirmed or likely occupational, including 7 (31.8%) from colleagues. Additionally, 5 (26.3%) of other infections were from colleagues outside the working facilities. 14 (63.6%) of occupational infections occurred while using a surgical mask. No occupational infections were found while using an FFP2/3 respirator and aerosol precautions while treating suspected or confirmed COVID-19 patients. Conclusions: While treating suspected or confirmed COVID-19 patients, HCWs should wear an FFP2/3 respirator and recommended PPE. Maintaining safety distances in the workplace and controlling infections between HCWs should be priorities to ensure safe working conditions.