Hydrogen Sulfide Protects Retinal Ganglion Cells Against Glaucomatous Injury In Vitro and In Vivo

作者：Liu Hanhan; Anders Fabian; Thanos Solon; Mann Carolina; Liu Aiwei; Grus Franz H; Pfeiffer Norbert; Prokosch Willing Verena^*

来源：Investigative Ophthalmology & Visual Science, 2017, 58(12): 5129-5141.

DOI：10.1167/iovs.17-22200

• hydrogen sulfide
• retinal ganglion cell
• elevated pressure
• glaucoma
• neuroprotection

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 lOP 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. lOP elevation caused significant RGC loss (P < 0.001); 3-mercaptosulfurtransferase, an H2S producing enzyme, showed a 3-fold upregulation within the retina after lOP 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.

• 出版日期2017-10