Mapping the origin and fate of myeloid cells in distinct compartments of the eye by single-cell profiling.

Similar to the brain, the eye is considered an immune-privileged organ where tissue-resident macrophages provide the major immune cell constituents. However, little is known about spatially restricted macrophage subsets within different eye compartments with regard to their origin, function, and fate during health and disease. Here, we combined single-cell analysis, fate mapping, parabiosis, and computational modeling to comprehensively examine myeloid subsets in distinct parts of the eye during homeostasis. This approach allowed us to identify myeloid subsets displaying diverse transcriptional states. During choroidal neovascularization, a typical hallmark of neovascular age-related macular degeneration (AMD), we recognized disease-specific macrophage subpopulations with distinct molecular signatures. Our results highlight the heterogeneity of myeloid subsets and their dynamics in the eye that provide new insights into the innate immune system in this organ which may offer new therapeutic targets for ophthalmological diseases.

Clinical Landscape of Central Serous Chorioretinopathy in Germany: Retina.net CSC Registry Report Number 1.

INTRODUCTION: The German Registry of central serous chorioretinopathy (CSC) collects data on CSC patients in a nationwide multicenter approach to analyze epidemiology, risk factors, clinical presentations, as well as diagnosis and treatment patterns. METHODS: In this multicenter cohort study, patients with CSC were enrolled in nine tertiary referral centers in Germany between January 2022 and June 2023. After consenting to the study, demographic data, risk factors, reported symptoms, best-corrected visual acuity (BCVA), funduscopic findings, disease severity, and diagnostic and treatment decisions were recorded and analyzed. RESULTS: A total of 539 eyes of 411 CSC patients were enrolled in this study including 308 males (75%) and 103 females (25%). Patients were predominantly of Caucasian origin and had a mean age of 55.5 years (IQR 41.0-70.0). 28% of eyes were classified as acute (<4 months duration) CSC, 28% as chronic (>4 months duration) CSC, 21% as inactive CSC, 11% as chronic atrophic CSC, and 12% as CSC with secondary CNV. 128 patients (31%) demonstrated bilateral CSC. The most common risk factors reported were psychological stress (52%), smoking (38%), arterial hypertension (38%), and a history of or current use of steroids (30%). Most frequently encountered symptoms included decreased visual acuity (76%), metamorphopsia (49%), relative scotoma (47%), blurred vision (19%), and dyschromatopsia (9%). The mean logMAR BCVA on initial examination was 0.2 (≈20/30, IQR 0.2-0.4) but showed significant variation with a tendency of lower BCVA in chronic cases. At the baseline visit, 74% of the overall cohort received no treatment, while 19% underwent local treatment and only 2% underwent systemic treatment. Of the local therapies, anti-VEGF injections were the most frequently performed procedure (33%, mainly for secondary CNV), followed by micropulse laser (28%), focal nonpulsed laser (23%), verteporfin photodynamic therapy (14%), and nonsteroidal anti-inflammatory eye drops (2%). Among intravitreal anti-VEGF agents, aflibercept was used most frequently, followed by bevacizumab and ranibizumab. CONCLUSION: This registry represents one of the largest cohorts of European patients with CSC to date. Patient age and the proportion of women were higher than expected and bilateral active disease was lower than anticipated, highlighting that neither age nor gender should be overemphasized when diagnosing CSC. Therapeutic interventions are heterogeneous and include verteporfin photodynamic therapy, micropulse laser, and anti-VEGF injections in case of secondary CNV.

Neuromuscular Fatigue Induced by a Mixed Martial Art Training Protocol.

ABSTRACT: Giboin, L-S and Gruber, M. Neuromuscular fatigue induced by a mixed martial art training protocol. J Strength Cond Res 36(2): 469-477, 2022-Mixed martial arts (MMA) is a full-contact sport whose popularity and professionalism are rapidly growing. However, the specific physiological demands of this sport have been only scarcely studied so far, and especially the amount or type of neuromuscular fatigue induced by an MMA bout remains completely unknown. We estimated neuromuscular fatigue of knee extensors muscles during and after an MMA training protocol designed to simulate the physiological demands of MMA competition in competitive practitioners (n = 9) with isometric maximal voluntary force (MVF), potentiated muscle twitch at rest (Ptw), and voluntary activation (VA). Bayesian linear mixed models showed that the training protocol induced a reduction of MVF, Ptw, and VA. Although the largest reduction across time of VA was smaller than the largest reduction of Ptw, an effect of VA, but not of Ptw, was found on MVF variation. The training protocol induced neuromuscular fatigue, with a larger peripheral (Ptw) than central component (VA). However, despite the large decrease in Ptw, force production capacity was related only to VA, indicating that central control might play an important role in the compensation of the peripheral fatigue components estimated with Ptw. This central compensation can most probably prevent a too large loss of muscle force during the training protocol.

Scrolling of the Donor Cornea in Dependence of Temperature and Osmolarity for Descemet Membrane Endothelial Keratoplasty. / Rollung der Spenderhornhaut in Abhängigkeit von Temperatur und Osmolarität für die Descemet Membrane endothelial Keratoplasty.

BACKGROUND: After preparation of a graft for Descemet membrane endothelial keratoplasty (DMEK), the diameter of the graft's scroll varies significantly. In particular, narrow scrolls may complicate DMEK surgery. In this study we investigated how temperature, osmolarity, and deswelling of the donor tissue influence scrolling diameter. MATERIAL AND METHODS: In this study we examined donor corneas that could not be used for transplantation. The diameter of the DMEK donor scrolls was measured after graft preparation by reflected light microscopy under different conditions: (1) The diameter of the roll was measured in Ringer's solution at temperatures of 5 °C, 24 °C and 35 °C. (2) To study the effect of different culture conditions we used 6% dextran-containing medium for 10 min, 20 min, 16 h and 24 h, and hyper- and hypoosmolar fluids (5% NaCl or aqua dest) for 5 min each. RESULTS: The median donors age was 62 years. The median endothelial cell density of the donor corneas was 1679 cells/mm2. The median diameter of the DMEK scroll was 1.35 mm in Ringer's solution at 24 °C (IQR, 1.04 - 1.89). In Ringer's solution at different temperatures, the scrolling diameter changed between 0.02 mm and 0.29 mm. The change in osmolarity resulted in a difference of 0.02 mm to 0.46 mm. Deswelling with dextran resulted in a change of scrolling diameter between 0.02 mm and 0.09 mm. SUMMARY: In this experimental case series, the diameter of the DMEK scroll did not change due to changes of temperature, osmolarity or deswelling. Influencing the graft's scroll to standardize and simplify the DMEK surgery remains an interesting goal for future studies.

The Upper Paralimbal Zone is Especially Susceptible to Ruptures Due to Blunt Trauma. / Die obere Paralimbalzone ist besonders anfällig für Berstungen durch stumpfe Traumata.

BACKGROUND: Globe ruptures are ophthalmological emergencies where the primary diagnosis using a slit lamp is often a challenge. OBJECTIVES: The retrospective case study aimed to characterise the predilection sites, the demographic profile and the causes of bursts due to blunt globe trauma. MATERIALS AND METHODS: The surgical plan of the Eye Centre of the Medical Centre (University of Freiburg) was electronically searched using the keyword "globe rupture" over a period of 18 years (2000 - 2018). This led to 350 hits, which were scrutinised by hand. 134 globe ruptures due to blunt globe trauma were then identified. RESULTS: The most common predilection sites were the upper nasal and the upper temporal paralimbal zones with 37 and 32% of the examined globe ruptures, respectively. The average age at the time of rupture was 60 (from 2 to 97) years. The median age was 62.5 years. 37% (49/134) of patients were female. The most frequent causes of accidents were falls (43%), "flying" wooden and metal objects (18%) and acts of violence (10%). CONCLUSIONS: Special attention should be paid to the upper paralimbal zone in the exploratory primary care of globe ruptures. If the rupture occurred due to "flying" wooden and metal objects, the posterior sclera burst most frequently. The epidemiological data suggest that targeted prevention against falls for individuals over 60 years and consistent wearing of protective eyewear when working with wood or metal could reduce the incidence of bulbar bursting. It was also noticeable that acts of violence were the third most frequent cause of rupture, although woman did not report that they were affected by this. Given the high occurrence of violence against women, shame and stigma may lead to an incorrect inquiry about the cause of the accident. This could be mitigated by training employees specifically to take a sensitive history.

Corticospinal properties are associated with sensorimotor performance in action video game players.

Notwithstanding the apparent demands regarding fine motor skills that are required to perform in action video games, the motor nervous system of players has not been studied systematically. In the present study, we hypothesized to find differences in sensorimotor performance and corticospinal characteristics between action video game players (Players) and Controls. We tested sensorimotor performance in video games tasks and used transcranial magnetic stimulation (TMS) to measure motor map, input-output (IO) and short intra-cortical inhibition (SICI) curves in the first dorsal interosseous (FDI) muscle of Players (n = 18) and Control (n = 18). Players scored higher in performance tests and had stronger SICI and higher motor evoked potential (MEP) amplitudes. Multiple linear regressions showed that Players and Control differed with respect to their relation between reaction time and corticospinal excitability. However, we did not find different motor map topography or different IO curves for Players when compared to Controls. Action video game players showed an increased efficiency of motor cortical inhibitory and excitatory neural networks. Players also showed a different relation of MEPs with reaction time. The present study demonstrates the potential of action video game players as an ideal population to study the mechanisms underlying visuomotor performance and sensorimotor learning.

Transcriptomic Characterization of Human Choroidal Neovascular Membranes Identifies Calprotectin as a Novel Biomarker for Patients with Age-Related Macular Degeneration.

Recent studies deciphering the transcriptional profile of choroidal neovascularization (CNV) in body donor eyes with neovascular age-related macular degeneration are limited by the time span from death to preservation and the associated 5'-RNA degradation. This study therefore used CNV and control specimens that were formalin-fixed and paraffin-embedded immediately after surgical extraction and analyzed them by a 3'-RNA sequencing approach. Transcriptome profiles were analyzed to estimate content of immune and stromal cells and to define disease-associated gene signatures by using statistical and bioinformatics methods. This study identified 158 differentially expressed genes (DEGs) that were significantly increased in CNV compared with control tissue. Cell type enrichment analysis revealed a diverse cellular landscape with an enrichment of endothelial cells, macrophages, T cells, and natural killer T cells in the CNV. Gene ontology enrichment analysis found that DEGs contributed to blood vessel development, extracellular structure organization, response to wounding, and several immune-related terms. The S100 calcium-binding proteins A8 (S100A8) and A9 (S100A9) emerged among the top DEGs, as confirmed by immunohistochemistry on CNV tissue and protein analysis of vitreous samples. This study provides a high-resolution RNA-sequencing-based transcriptional signature of human CNV, characterizes its compositional pattern of immune and stromal cells, and reveals S100A8/A9 to be a novel biomarker and promising target for therapeutics and diagnostics directed at age-related macular degeneration.

MS-EmpiRe Utilizes Peptide-level Noise Distributions for Ultra-sensitive Detection of Differentially Expressed Proteins.

Mass spectrometry based proteomics is the method of choice for quantifying genome-wide differential changes of protein expression in a wide range of biological and biomedical applications. Protein expression changes need to be reliably derived from many measured peptide intensities and their corresponding peptide fold changes. These peptide fold changes vary considerably for a given protein. Numerous instrumental setups aim to reduce this variability, whereas current computational methods only implicitly account for this problem. We introduce a new method, MS-EmpiRe, which explicitly accounts for the noise underlying peptide fold changes. We derive data set-specific, intensity-dependent empirical error fold change distributions, which are used for individual weighing of peptide fold changes to detect differentially expressed proteins (DEPs).In a recently published proteome-wide benchmarking data set, MS-EmpiRe doubles the number of correctly identified DEPs at an estimated FDR cutoff compared with state-of-the-art tools. We additionally confirm the superior performance of MS-EmpiRe on simulated data. MS-EmpiRe requires only peptide intensities mapped to proteins and, thus, can be applied to any common quantitative proteomics setup. We apply our method to diverse MS data sets and observe consistent increases in sensitivity with more than 1000 additional significant proteins in deep data sets, including a clinical study over multiple patients. At the same time, we observe that even the proteins classified as most insignificant by other methods but significant by MS-EmpiRe show very clear regulation on the peptide intensity level. MS-EmpiRe provides rapid processing (< 2 min for 6 LC-MS/MS runs (3 h gradients)) and is publicly available under github.com/zimmerlab/MS-EmpiRe with a manual including examples.

The performance of balance exercises during daily tooth brushing is not sufficient to improve balance and muscle strength in healthy older adults.

BACKGROUND: High prevalence rates have been reported for physical inactivity, mobility limitations, and falls in older adults. Home-based exercise might be an adequate means to increase physical activity by improving health- (i.e., muscle strength) and skill-related components of physical fitness (i.e., balance), particularly in times of restricted physical activity due to pandemics. OBJECTIVE: The objective of this study was to examine the effects of home-based balance exercises conducted during daily tooth brushing on measures of balance and muscle strength in healthy older adults. METHODS: Fifty-one older adults were randomly assigned to a balance exercise group (n = 27; age: 65.1 ± 1.1 years) or a passive control group (n = 24; age: 66.2 ± 3.3 years). The intervention group conducted balance exercises over a period of eight weeks twice daily for three minutes each during their daily tooth brushing routine. Pre- and post-intervention, tests were included for the assessment of static steady-state balance (i.e., Romberg test), dynamic steady-state balance (i.e., 10-m single and dual-task walk test using a cognitive and motor interference task), proactive balance (i.e., Timed-Up-and-Go Test [TUG], Functional-Reach-Test [FRT]), and muscle strength (i.e., Chair-Rise-Test [CRT]). RESULTS: Irrespective of group, the statistical analysis revealed significant main effects for time (pre vs. post) for dual-task gait speed (p < .001, 1.12 ≤ d ≤ 2.65), TUG (p < .001, d = 1.17), FRT (p = .002, d = 0.92), and CRT (p = .002, d = 0.94) but not for single-task gait speed and for the Romberg-Test. No significant group × time interactions were found for any of the investigated variables. CONCLUSIONS: The applied lifestyle balance training program conducted twice daily during tooth brushing routines appears not to be sufficient in terms of exercise dosage and difficulty level to enhance balance and muscle strength in healthy adults aged 60-72 years. Consequently, structured balance training programs using higher exercise dosages and/or more difficult balance tasks are recommended for older adults to improve balance and muscle strength.

Daily 30-min exposure to artificial gravity during 60 days of bed rest does not maintain aerobic exercise capacity but mitigates some deteriorations of muscle function: results from the AGBRESA RCT.

PURPOSE: Spaceflight impairs physical capacity. Here we assessed the protective effect of artificial gravity (AG) on aerobic exercise capacity and muscle function during bed rest, a spaceflight analogue. METHODS: 24 participants (33 ± 9 years, 175 ± 9 cm, 74 ± 10 kg, 8 women) were randomly allocated to one of three groups: continuous AG (cAG), intermittent AG (iAG) or control (CTRL). All participants were subjected to 60 days of six-degree head-down tilt bed rest, and subjects of the intervention groups completed 30 min of centrifugation per day: cAG continuously and iAG for 6 × 5 min, with an acceleration of 1g at the center of mass. Physical capacity was assessed before and after bed rest via maximal voluntary contractions, cycling spiroergometry, and countermovement jumps. RESULTS: AG had no significant effect on aerobic exercise capacity, flexor muscle function and isometric knee extension strength or rate of force development (RFD). However, AG mitigated the effects of bed rest on jumping power (group * time interaction of the rmANOVA p < 0.001; iAG - 25%, cAG - 26%, CTRL - 33%), plantar flexion strength (group * time p = 0.003; iAG - 35%, cAG - 31%, CTRL - 48%) and plantar flexion RFD (group * time p = 0.020; iAG - 28%, cAG - 12%, CTRL - 40%). Women showed more pronounced losses than men in jumping power (p < 0.001) and knee extension strength (p = 0.010). CONCLUSION: The AG protocols were not suitable to maintain aerobic exercise capacity, probably due to the very low cardiorespiratory demand of this intervention. However, they mitigated some losses in muscle function, potentially due to the low-intensity muscle contractions during centrifugation used to avoid presyncope.