Excessive reactive oxygen species (ROS) contribute to damage of retinal cells and the development of retinal diseases including age‐related macular degeneration (AMD). ROS result in increased metabolites of lipoxygenases (LOXs), which react with ROS to induce lipid peroxidation and may lead to ferroptosis. In this study, the effect of 5‐LOX inhibition on alleviating ROS‐induced cell death was evaluated using sodium iodate (NaIO3) in the retinal pigment epithelium (RPE) cell line ARPE‐19 and a mouse model investigating oxidative stress in AMD. We demonstrated that NaIO3 induced cell death in the RPE cells through mechanisms including ferroptosis. Inhibition of 5‐LOX with specific inhibitor, Zileuton, or siRNA knockdown of ALXO5 mitigated NaIO3‐induced lipid peroxidation, mitochondrial damage, DNA impairment, and cell death in ARPE‐19 cells. Additionally, in the mouse model, pretreatment with Zileuton reduced the NaIO3‐induced lipid peroxidation of RPE cells, cell death in the photoreceptor layer of the retina, inflammatory responses, and degeneration of both the neuroretina and RPE monolayer cells. Our results suggest that 5‐LOX plays a crucial role in ROS‐induced cell death in the RPE and that regulating 5‐LOX activity could be a useful approach to control ROS and ferroptosis‐induced damage, which promote degeneration in retinal diseases.
To report the epidemiology and clinical features of viral anterior uveitis in patients in southern Taiwan. A retrospective, case series study. HLA-B27 negative anterior uveitis patients with increased intraocular pressure or corneal edema seen at Kaohsiung Chang Gung Memorial Hospital from January 1, 2007 to January 31, 2018 had their aqueous sent for polymerase chain reaction analysis. Their records were reviewed for demographic data, ocular findings, and laboratory results. In the aqueous samples obtained from 102 eligible eyes, 42 eyes were herpesviridae-positive, which included 9 with herpes simplex virus (8.8%), 5 with varicella-zoster virus (4.9%), 27 with cytomegalovirus (26.5%), and 1 with Epstein-Barr virus (1%). Herpesviridae-positive patients were more likely to be male, and have glaucoma. Glaucoma and pseudophakic eyes were significantly associated with CMV-positive eyes. PCR analysis of the anterior chamber fluid is important for the confirmation of the diagnosis of viral anterior uveitis. Cytomegalovirus anterior uveitis is not uncommon in patients in southern Taiwan, and it may follow an uneventful cataract extraction in immunocompetent patients.
The diagnosis and monitoring of Sjögren syndrome (SS) is often difficult, requiring a multidisciplinary approach with invasive procedures. Our aim is to elucidate the tear protein alterations of dry eye disease (DED) with primary SS (pSS) and secondary SS (sSS) with the long-term instillation of eyedrops. We collected clinical demographics and tear fluid (TF) samples from DED patients with no autoimmune diseases (non-SS-DED), pSS-DED, and sSS-DED patients, followed by TF screening with tandem mass tagging-labeling gel-free proteomics assay. Bioinformatic analysis via Ingenuity Pathway Analysis was used to identify functional pathways and interacting networks. Validation of candidate proteins with enzyme-linked immunosorbent assay on the tear samples was done. The top functional pathways of the two comparisons (sSS-DED vs. pSS-DED and sSS-DED vs. non-SS-DED) were both associated with inflammation and stress-related signaling. After constructing an interaction network model with the selected candidate proteins, five proteins were identified. A Disintegrin and Metalloproteinase domain-containing protein 10 (ADAM10) was found to be an important candidate biomarker in all groups, followed by epidermal growth factor (EGF) in TF. This study revealed novel DED markers, ADAM10 and EGF, in differentiating between primary and secondary SS patients from tears by in-depth proteomic analysis.
This study aims at determining the thickness of the tear lipid layer (LL) observed from a placido-disc-based tear film analyzer. We prospectively collected reflections of placido-disk LL images using a tear film analyzer (Keratograph® 5M, Oculus) from subjects with dry eye symptoms. The LL thickness (LLT) over the inferior half of the cornea was estimated with the use of interference color analysis and the preprocessing of images with and without ring segmentation were obtained and analyzed. Moreover, LLTs before and after 1 h of applying topical ointment (Duratears, Alcon) were compared to validate the estimation of LLT. Our results suggested that the tear LLT can be assessed using a placido-disk-based tear film analyzer and interference color analysis. We verified a high correlation between non-segmented and segmented LL images and estimated LLT increase after applying ointment. In addition, we concluded that LLT can be evaluated by direct interference analysis without segmentation preprocessing.
5 December 2022 in Biochemical and Biophysical Research Communications
Clinical competencies consisting of skills, knowledge, and communication techniques should be acquired by all medical graduates to optimize healthcare quality. However, transitioning from observation to hands-on learning in clinical competencies poses a challenge to medical students. The aim of this study is to evaluate the impact of a novel interactive multimedia eBook curriculum in clinical competency training. Ninety-six medical students were recruited. Students in the control group (n = 46) were taught clinical competencies via conventional teaching, while students in the experimental group (n = 50) were taught with conventional teaching plus interactive multimedia eBooks. The outcomes of clinical competencies were evaluated using Objective Structured Clinical Examination (OSCE) scores, and feedback on their interactive eBook experiences was obtained. In the experimental group, the average National OSCE scores were not only higher than the control group (214.8 vs. 206.5, p < 0.001), but also showed a quicker improvement when comparing between three consecutive mock OSCEs (p < 0.001). In response to open-ended questions, participants emphasized the importance of eBooks in improving their abilities and self-confidence when dealing with ‘difficult’ patients. Implementing interactive multimedia eBooks could prompt a more rapid improvement in clinical skill performance to provide safer healthcare, indicating the potential of our innovative module in enhancing clinical competencies.