Immunomodulatory and Antioxidant Drugs in Glaucoma Treatment.

Glaucoma, a group of diseases characterized by progressive retinal ganglion cell loss, cupping of the optic disc, and a typical pattern of visual field defects, is a leading cause of severe visual impairment and blindness worldwide. Elevated intraocular pressure (IOP) is the leading risk factor for glaucoma development. However, glaucoma can also develop at normal pressure levels. An increased susceptibility of retinal ganglion cells to IOP, systemic vascular dysregulation, endothelial dysfunction, and autoimmune imbalances have been suggested as playing a role in the pathophysiology of normal-tension glaucoma. Since inflammation and oxidative stress play a role in all forms of glaucoma, the goal of this review article is to present an overview of the inflammatory and pro-oxidant mechanisms in the pathophysiology of glaucoma and to discuss immunomodulatory and antioxidant treatment approaches.

Gender Differences and the Impact of Partnership and Children on Quality of Life During the COVID-19 Pandemic.

Objectives: The COVID-19 pandemic and its protective measures have changed the daily lives of families and may have affected quality of life (QoL). The aim of this study was to analyze gender differences in QoL and to examine individuals living in different partnership and family constellations. Methods: Data from the Gutenberg COVID-19 cohort study (N = 10,250) with two measurement time points during the pandemic (2020 and 2021) were used. QoL was assessed using the EUROHIS-QOL questionnaire. Descriptive analyses and autoregressive regressions were performed. Results: Women reported lower QoL than men, and QoL was significantly lower at the second measurement time point in both men and women. Older age, male gender, no migration background, and higher socioeconomic status, as well as partnership and children (especially in men), were protective factors for QoL. Women living with children under 14 and single mothers reported significantly lower QoL. Conclusion: Partnership and family were protective factors for QoL. However, women with young children and single mothers are vulnerable groups for lower QoL. Support is especially needed for women with young children.

Short-Term Omega-3 Supplementation Modulates Novel Neurovascular and Fatty Acid Metabolic Proteome Changes in the Retina and Ophthalmic Artery of Mice with Targeted Cyp2c44 Gene Deletion.

Cytochrome P450 (CYP) gene mutations are a common predisposition associated with glaucoma. Although the molecular mechanisms are largely unknown, omega-3 polyunsaturated fatty acids (ω-3 PUFA) and their CYP-derived bioactive mediators play crucial roles in the ocular system. Here, we elucidated the proteome and cell-signalling alterations attributed to the main human CYP2C gene deficiency using a homologous murine model (Cyp2c44-/-), and unravelled the effects of acute ω-3 PUFA supplementation in two ocular vascular beds comprising the retrobulbar ophthalmic artery (OA) and retina (R). Male Cyp2c44-/- mice (KO) and their floxed littermates (WT) were gavaged daily for 7 days with 0.01 mL/g of ω-3 PUFA composed of menhaden fish oil. Another group in respective strains served as vehicle-treated controls. OA and R were isolated at day 8 post-treatment (n = 9/group) and subjected to mass spectrometry (MS)-based proteomics and in silico bioinformatics analyses. Cyp2c44-/- resulted in significant detrimental proteome changes associated with compromised vascular integrity and degeneration in the OA and R, respectively. However, notable changes in the OA after ω-3 PUFA intake were associated with the maintenance of intercellular junctional and endothelial cell functions, as well as activation of the fatty acid metabolic pathway in the KO mice. Conversely, ω-3 PUFA supplementation profoundly influenced the regulation of a large majority of retinal proteins involved in the preservation of neuronal and phototransduction activities in WT mice, namely synaptophysin, phosducin and guanylate cyclase-1, while significantly abrogating degenerative processes in the KO mice via the regulation of, namely, synaptotagmin-1 and beta-crystallin B2. In gist, this study demonstrated that dietary supplementation with ω-3 PUFA for a short period of seven days regulated specific neuro-vasculoprotective mechanisms to preserve the functionality of the OA and R in the absence of Cyp2c44. The potential adjunct use of ω-3 PUFA for glaucoma therapy needs further investigation.

[Psychosomatic medicine in the Gutenberg Health Study (GHS) - research questions, measurement instruments, selected results]. / Psychosomatische Medizin in der Gutenberg- Gesundheitsstudie (GHS) ­ Fragestellungen, Messverfahren, ausgewählte Ergebnisse.

Psychosomatic medicine in the Gutenberg Health Study (GHS) - research questions, measurement instruments, selected results Goal: Main questions from the Gutenberg Health Study (GHS) related to psychosomatic medicine are presented: (1) Prevalence and incidence of mental illnesses, (2) Sex-specific risk- and protective factors for mental health, (3) Interplay between psychological and somatic diseases and (4) methodical-psychometric developments. Methods: The GHS is an ongoing, prospective and interdisciplinary cohort study in Mainz. The comprehensive examinations include psychological characteristics and clinical and laboratory tests. 15010 respondents were selected in the baseline study from 2007 until 2012 and re-examined after 2.5 years and 5 years. Results: Of the first 5000 respondents in the baseline study 413 women (8.7 %) and 276 men (5.8 %) indicated depressive symptoms (PHQ-9 > = 10). After five years, half of the participants with depressive symptoms at baseline also indicated depressive symptoms five years later. Risk factors for men were a lack of social support, for women smoking and Type D personality. The proportion of new cases of depression at follow-up was 4.4 %. Risk factors were symptoms of anxiety, Type D, smoking and comorbid cancer. Protective were age and social support. Findings on the association of physical and mental disorders and their behavioral and biological links (atherosclerosis, inflammation) are presented. Conclusions: Prospective assessment of biological, psychological and social parameters offers the possibility to study their interplay in the development of mental and somatic illnesses.

Iron deficiency is a common disorder in general population and independently predicts all-cause mortality: results from the Gutenberg Health Study.

BACKGROUND: Iron deficiency is now accepted as an independent entity beyond anemia. Recently, a new functional definition of iron deficiency was proposed and proved strong efficacy in randomized cardiovascular clinical trials of intravenous iron supplementation. Here, we characterize the impact of iron deficiency on all-cause mortality in the non-anemic general population based on two distinct definitions. METHODS: The Gutenberg Health Study is a population-based, prospective, single-center cohort study. The 5000 individuals between 35 and 74 years underwent baseline and a planned follow-up visit at year 5. Tested definitions of iron deficiency were (1) functional iron deficiency-ferritin levels below 100 µg/l, or ferritin levels between 100 and 299 µg/l and transferrin saturation below 20%, and (2) absolute iron deficiency-ferritin below 30 µg/l. RESULTS: At baseline, a total of 54.5% of participants showed functional iron deficiency at a mean hemoglobin of 14.3 g/dl; while, the rate of absolute iron deficiency was 11.8%, at a mean hemoglobin level of 13.4 g/dl. At year 5, proportion of newly diagnosed subjects was 18.5% and 4.8%, respectively. Rate of all-cause mortality was 7.2% (n = 361); while, median follow-up was 10.1 years. After adjustment for hemoglobin and major cardiovascular risk factors, the hazard ratio with 95% confidence interval of the association of iron deficiency with mortality was 1.3 (1.0-1.6; p = 0.023) for the functional definition, and 1.9 (1.3-2.8; p = 0.002) for absolute iron deficiency. CONCLUSIONS: Iron deficiency is very common in the apparently healthy general population and independently associated with all-cause mortality in the mid to long term.

KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern.

BACKGROUNDThe presence of an early repolarization pattern (ERP) on the surface ECG is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait, but molecular genetic determinants are unknown.METHODSTo identify genetic susceptibility loci for ERP, we performed a GWAS and meta-analysis in 2,181 cases and 23,641 controls of European ancestry.RESULTSWe identified a genome-wide significant (P < 5 × 10-8) locus in the potassium voltage-gated channel subfamily D member 3 (KCND3) gene that was successfully replicated in additional 1,124 cases and 12,510 controls. A subsequent joint meta-analysis of the discovery and replication cohorts identified rs1545300 as the lead SNP at the KCND3 locus (OR 0.82 per minor T allele, P = 7.7 × 10-12) but did not reveal additional loci. Colocalization analyses indicate causal effects of KCND3 gene expression levels on ERP in both cardiac left ventricle and tibial artery.CONCLUSIONSIn this study, we identified for the first time to our knowledge a genome-wide significant association of a genetic variant with ERP. Our findings of a locus in the KCND3 gene provide insights not only into the genetic determinants but also into the pathophysiological mechanism of ERP, discovering a promising candidate for functional studies.FUNDINGThis project was funded by the German Center for Cardiovascular Research (DZHK Shared Expertise SE081 - STATS). For detailed funding information per study, see the Supplemental Acknowledgments.

Klassifikation, Genetik und Epidemiologie der Glaukome.

Glaucoma is a heterogeneous group of diseases which all share retinal ganglion cell loss leading to a typical optic disc cupping and characteristic visual field defects. Glaucoma is the leading cause of irreversible blindness affecting 8.4 million people. In 2013, 65 million people suffered from glaucoma worldwide and the number will increase to about 112 million in 2040. This review provides an overview about the classification and genetic basics in glaucoma.