Hydrogen Sulfide Contributes to Retinal Neovascularization in Ischemia-Induced Retinopathy.
Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule with significant pathophysiological importance, but its role in retinal neovascular diseases is unknown. Hydrogen sulfide is generated from L-cysteine by cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and/or 3-mercaptopyruvate sulfurtransferase (3-MST). The aim of this study was to investigate the role of H2S in retinal neovascularization (NV) in ischemia-induced retinopathy.



Studies were performed in a murine model of oxygen-induced retinopathy (OIR). Hydrogen sulfide was detected with a fluorescent assay. Western blots and immunohistochemistry were used to assess the changes of H2S-producing enzymes. Gene deletion and pharmacologic inhibition were used to investigate the role of H2S in retinal NV.



Hydrogen sulfide production was markedly increased in retinas from OIR mice compared with those from room air (RA) controls. Cystathionine-β-synthase and CSE were significantly increased in OIR retinas, whereas 3-MST was not changed. Cystathionine-β-synthase was expressed throughout the neuronal retina and upregulated in neurons and glia during OIR. Cystathionine-γ-lyase was also localized to multiple retinal layers. Its immunoreactivity was prominently increased in neovascular tufts in OIR. Pharmacologic inhibition of CBS/CSE or genetic deletion of CSE significantly reduced retinal NV in OIR.



Our data indicate that the H2S-generating enzymes/H2S contributes to retinal NV in ischemia-induced retinopathy and suggest that blocking this pathway may provide novel therapeutic approaches for the treatment of proliferative retinopathy.
Center for Biomedical Engineering, The University of Texas Medical Branch, Galveston, Texas, United States 2Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch, Galveston, Texas, United States 3Neuroscience & Cell Biolo.
David
D
Gersztenkorn
Anesthesiology, The University of Texas Medical Branch, Galveston, Texas, United States.
Ciro
C
Coletta
Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch, Galveston, Texas, United States.
Shuang
S
Zhu
Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch, Galveston, Texas, United States.
Yonju
Y
Ha
Center for Biomedical Engineering, The University of Texas Medical Branch, Galveston, Texas, United States.
Hua
H
Liu
Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch, Galveston, Texas, United States.
Hongyan
H
Tie
Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, Texas, United States.
Jia
J
Zhou
Anesthesiology, The University of Texas Medical Branch, Galveston, Texas, United States.
Csaba
C
Szabo
Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch, Galveston, Texas, United States 3Neuroscience & Cell Biology, The University of Texas Medical Branch, Galveston, Texas, United States.
Wenbo
W
Zhang
Center for Biomedical Engineering, The University of Texas Medical Branch, Galveston, Texas, United States 2Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch, Galveston, Texas, United States.
Massoud
M
Motamedi
D000818:Animals; D015153:Blotting, Western; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D004195:Disease Models, Animal; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007150:Immunohistochemistry; D007511:Ischemia / Q000378:metabolism*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism; D009434:Neural Pathways / Q000502:physiology; D015861:Retinal Neovascularization / Q000378:metabolism*; D013466:Sulfurtransferases / Q000378:metabolism
D013466:Sulfurtransferases; C021550:3-mercaptopyruvate sulphurtransferase; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide