Dysregulated Retinoic Acid Signaling in the Pathogenesis of Pseudoexfoliation Syndrome.

Pseudoexfoliation (PEX) syndrome, a stress-induced fibrotic matrix process, is the most common recognizable cause of open-angle glaucoma worldwide. The recent identification of PEX-associated gene variants uncovered the vitamin A metabolic pathway as a factor influencing the risk of disease. In this study, we analyzed the role of the retinoic acid (RA) signaling pathway in the PEX-associated matrix metabolism and evaluated its targeting as a potential candidate for an anti-fibrotic intervention. We provided evidence that decreased expression levels of RA pathway components and diminished RA signaling activity occur in an antagonistic crosstalk with TGF-ß1/Smad signaling in ocular tissues and cells from PEX patients when compared with age-matched controls. Genetic and pharmacologic modes of RA pathway inhibition induced the expression and production of PEX-associated matrix components by disease-relevant cell culture models in vitro. Conversely, RA signaling pathway activation by natural and synthetic retinoids was able to suppress PEX-associated matrix production and formation of microfibrillar networks via antagonization of Smad-dependent TGF-ß1 signaling. The findings indicate that deficient RA signaling in conjunction with hyperactivated TGF-ß1/Smad signaling is a driver of PEX-associated fibrosis, and that restoration of RA signaling may be a promising strategy for anti-fibrotic intervention in patients with PEX syndrome and glaucoma.

Associations of Personality, Physical and Mental Health with Voice Range Profiles.

OBJECTIVES: There is evidence in the literature that voice characteristics are linked to mental and physical health. The aim of this explorative study was to determine associations between voice parameters measured by a voice range profile (VRP) and personality, mental and physical health. STUDY DESIGN: Cross-sectional population-based study. METHODS: As part of the LIFE-Adult-Study, 2639 individuals aged 18-80 years, randomly sampled from the general population, completed both speaking and singing voice tasks and answered questionnaires on depression, anxiety, life satisfaction, personality and quality of life. The voice parameters used were fundamental frequency, sound pressure level, their ranges and maximum phonation time. The associations were examined with the help of correlation and regression analyses. RESULTS: Wider ranges between the lowest and highest frequency, between the lowest and highest sound pressure level and longer maximum phonation time were significantly correlated with extraversion and quality of life in both sexes, as well as openness and agreeableness in women. Smaller ranges and shorter maximum phonation time were significantly correlated with depression. Neuroticism in men was inversely correlated with the maximum phonation time. In the speaking VRP, the associations for sound pressure level were more pronounced than for the fundamental frequency. The same was true in reverse for the singing VRP. Few associations were found for anxiety, life satisfaction and conscientiousness. CONCLUSIONS: Weak associations between voice parameters derived from the VRP and mental and physical health, as well as personality were seen in this exploratory study. The results indicate that the VRP measurements in a clinical context are not significantly affected by these parameters and thus are a robust measurement method for voice parameters.