Abstract
Purpose :
Hydrogen sulfide (H2S) is a gas and neurotransmitter endogenously produced within endothelial cells. Recently, cell protective properties within the central nervous system and cardiovascular system have been proposed. Its role in glaucoma remains unknown. Purpose of our study was to 1) analyse the expression changes of H2S in an experimental animal glaucoma model and 2) to analyze its potential neuroprotective effect on retinal ganglion cells (RGC) due to elevated pressure in vitro and in vivo.
Methods :
Experimental glaucoma was induced in adult Sprague Dawley rats by vein cauterization (n=23).Changes in H2S and 3-mercaptopyruvate expression within the retina was analyzed via label-free mass spectrometry in retina with elevated IOP. In vitro, organotypic retinal explants were cultured for two days without elevated pressure or under controlled elevated hydrostatic pressure with and without addition of GYY4137 (1 nM-10 μM), a slow-releasing H2S donor to medium. H2S in the best concentration was injected intravitreally in animals with elevated IOP. RGC survival was measured by BRN3A staining. RNFL thickness and vessel diameters were measured in vivo by Spectralis-OCT (Heidelberg Engineering). Multiple comparisons were made by ANOVA. p< 0.05 was set as statistically significant.
Results :
IOP was significantly increased with a significant ganglion cell loss over time (p< 0.0001). H2S showed a significant downregulation after 7 weeks of elevated intraocular pressure compared to controls (p< 0.05) and 3-mercaptopyruvate sulfurtransferase a significant upregulation in retina of glaucomatous animals. Within the concentration range of 1 nM to 100 nM,GYY4137 could significantly improve RGC survival under elevated hydrostatic pressure in vitro (p< 0.005), while higher doses remained toxic. In vivo intravitreal addition of H2S preserved RGCs from IOP induced cell death. Vessel diameters around the optic nerve head measured by OCT appeared enlarged.
Conclusions :
In this study, H2S gave evidence to be potentially neuroprotective in retinal explants and retina of glaucomatous animals. H2S appears to play a key role in experimental glaucoma and thus the administration of H2S could be a potential treatment approach in glaucoma therapy.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.