Inhibitory action of novel hydrogen sulfide donors on bovine isolated posterior ciliary arteries

This is the author’s version of a work that was accepted for publication in Experimental Eye Research. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Experiemental Eye Research, Vol. 134, (2015) doi:10.1016/j.exer.2015.04.001.In the present study, we investigate the inhibitory effect of novel H2S donors, AP67 and AP72 on isolated bovine posterior ciliary arteries (PCAs) under conditions of tone induced by an adrenoceptor agonist. Furthermore, we examined the possible mechanisms underlying the AP67- and AP72-induced relaxations. Isolated bovine PCA were set up for measurement of isometric tension in organ baths containing oxygenated Krebs solution. The relaxant action of H2S donors was studied on phenylephrine-induced tone in the absence or presence of enzyme inhibitors for the following pathways: cyclooxygenase (COX); H2S; nitric oxide and the ATP-sensitive K(+) (KATP) channel. The H2S donors, NaHS (1 nM - 10 μM), AP67 (1 nM - 10 μM) and AP72 (10 nM - 1 μM) elicited a concentration-dependent relaxation of phenylephrine-induced tone in isolated bovine PCA. While the COX inhibitor, flurbiprofen (3 μM) blocked significantly (p < 0.05) the inhibitory response elicited by AP67, it had no effect on relaxations induced by NaHS and AP72. Both aminooxyacetic acid (30 μM) and propargylglycine (1 mM), enzyme inhibitors of H2S biosynthesis caused significant (p < 0.05) rightward shifts in the concentration-response curve to AP67 and AP72. Furthermore, the KATP channel antagonist, glibenclamide (300 μM) and the NO synthase inhibitor, l-NAME (100 μM) significantly attenuated (p < 0.05) the relaxation effect induced by AP67 and AP72 on PCA. We conclude that H2S donors can relax pre-contracted isolated bovine PCA, an effect dependent on endogenous production of H2S. The inhibitory action of only AP67 on pre-contracted PCA may involve the production of inhibitory endogenous prostanoids. Furthermore, the observed inhibitory action of H2S donors on PCA may depend on the endogenous biosynthesis of NO and by an action of KATP channels.National Institutes of Health/National Eye Institute Gran

Traffic-related air pollution and spectacles use in schoolchildren

Purpose: To investigate the association between exposure to traffic-related air pollution and use of spectacles (as a surrogate measure for myopia) in schoolchildren. Methods: We analyzed the impact of exposure to NO2 and PM2.5 light absorbance at home (predicted by land-use regression models) and exposure to NO2 and black carbon (BC) at school (measured by monitoring campaigns) on the use of spectacles in a cohort of 2727 schoolchildren (7–10 years old) in Barcelona (2012–2015). We conducted cross-sectional analyses based on lifelong exposure to air pollution and prevalent cases of spectacles at baseline data collection campaign as well as longitudinal analyses based on incident cases of spectacles use and exposure to air pollution during the three-year period between the baseline and last data collection campaigns. Logistic regression models were developed to quantify the association between spectacles use and each of air pollutants adjusted for relevant covariates. Results: An interquartile range increase in exposure to NO2 and PM2.5 absorbance at home was respectively associated with odds ratios (95% confidence intervals (CIs)) for spectacles use of 1.16 (1.03, 1.29) and 1.13 (0.99, 1.28) in cross-sectional analyses and 1.15 (1.00, 1.33) and 1.23 (1.03, 1.46) in longitudinal analyses. Similarly, odds ratio (95% CIs) of spectacles use associated with an interquartile range increase in exposures to NO2 and black carbon at school was respectively 1.32 (1.09, 1.59) and 1.13 (0.97, 1.32) in cross-sectional analyses and 1.12 (0.84, 1.50) and 1.27 (1.03, 1.56) in longitudinal analyses. These findings were robust to a range of sensitivity analyses that we conducted. Conclusion: We observed increased risk of spectacles use associated with exposure to traffic-related air pollution. These findings require further confirmation by future studies applying more refined outcome measures such as quantified visual acuity and separating different types of refractive errors.The research leading to these results has received funding from the European Research Council under the ERC Grant Agreement number 268479 –the BREATHE project. Payam Dadvand is funded by a Ramón y Cajal fellowship (RYC-2012-10995) awarded by the Spanish Ministry of Economy and Competitiveness