Authors:	Liu, Hanhan Anders, Fabian Thanos, Solon Mann, Carolina Liu, Aiwei Grus, Franz-Hermann Pfeiffer, Norbert Prokosch-Willing, Verena
Title:	Hydrogen sulfide protects retinal ganglion cells against glaucomatous injury in vitro and in vivo
Online publication date:	11-Jul-2022
Year of first publication:	2017
Language:	english
Abstract:	Purpose: Hydrogen sulfide (H2S) is recognized as a novel third signaling molecule and gaseous neurotransmitter. Recently, cell protective properties within the central nervous and cardiovascular system have been proposed. Our purpose was to analyze the expression and neuroprotective effects of H2S in experimental models of glaucoma. Methods: Elevated IOP was induced in Sprague-Dawley rats by means of episcleral vein cauterization. After 7 weeks, animals were killed and the retina was analyzed with label-free mass spectrometry. In vitro, retinal explants were exposed to elevated hydrostatic pressure or oxidative stress (H2O2), with and without addition of a slow-releasing H2S donor Morpholin-4-ium-methoxyphenyl-morpholino-phosphinodithioate (GYY4137). In vivo, GYY4137 was injected intravitreally in animals with acute ischemic injury or optic nerve crush. Brn3a+ retinal ganglion cells (RGCs) were counted in retinal flat mounts and compared. Optical coherence tomography (OCT) was performed to examine the vessels. Comparisons were made by t-test and ANOVA (P < 0.05). Results: IOP elevation caused significant RGC loss (P < 0.001); 3-mercaptosulfurtransferase, an H2S producing enzyme, showed a 3-fold upregulation within the retina after IOP elevation. GYY4137 protected RGCs against elevated pressure and oxidative stress in vitro depending on the concentration used (P < 0.005). In vivo, intravitreal administration of GYY4137 preserved RGCs from acute ischemic injury and optic nerve crush (P < 0.0001). Retinal vessel diameters enlarged after intravitreal GYY4137 injection (P < 0.0001). Conclusions: H2S is specifically regulated in experimental glaucoma. By scavenging reactive oxygen species and dilating retinal vessels, H2S may protect RGCs from pressure and oxidative stress–induced RGC loss in vitro and in vivo. Therefore, H2S might be a novel neuroprotectant in glaucoma.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7353
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY-NC-ND
Information on rights of use:	https://creativecommons.org/licenses/by-nc-nd/4.0/
Journal:	Investigative ophthalmology & visual science 58 12
Pages or article number:	5129 5141
Publisher:	ARVO
Publisher place:	Rockville, Md.
Issue date:	2017
ISSN:	1552-5783 0146-0404
Publisher URL:	http://dx.doi.org/10.1167/iovs.17-22200
Publisher DOI:	10.1167/iovs.17-22200
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)