Hydrogen sulfide contributes to retinal neovascularization in Ischemia-Induced retinopathy

David Gersztenkorn, Ciro Coletta, Shuang Zhu, Yonju Ha, Hua Liu, Hongyan Tie, Jia Zhou, Csaba Szabo, Wenbo Zhang, Massoud Motamedi

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


PURPOSE. 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), cystathioninec-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. METHODS. 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. RESULTS. 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-bsynthase 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. CONCLUSIONS. 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.

Original languageEnglish (US)
Pages (from-to)3002-3009
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Issue number7
StatePublished - Jun 2016


  • Hydrogen sulfide
  • Neovascularization
  • Oxygen-induced retinopathy

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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