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 journalArticle

9 Citations (Scopus)

Abstract

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
Volume57
Issue number7
DOIs
StatePublished - Jun 1 2016

Fingerprint

Retinal Neovascularization
Hydrogen Sulfide
Lyases
Cystathionine
Ischemia
Oxygen
Retina
Cysteine Synthase
Retinal Diseases
Gene Deletion
Enzymes
Neuroglia
Cysteine
Western Blotting
Immunohistochemistry
Air
Neurons
Therapeutics

Keywords

  • Hydrogen sulfide
  • Neovascularization
  • Oxygen-induced retinopathy

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Hydrogen sulfide contributes to retinal neovascularization in Ischemia-Induced retinopathy. / Gersztenkorn, David; Coletta, Ciro; Zhu, Shuang; Ha, Yonju; Liu, Hua; Tie, Hongyan; Zhou, Jia; Szabo, Csaba; Zhang, Wenbo; Motamedi, Massoud.

In: Investigative Ophthalmology and Visual Science, Vol. 57, No. 7, 01.06.2016, p. 3002-3009.

Research output: Contribution to journalArticle

@article{2fcf0d4ee4e24b83b0f52ca1094f9760,
title = "Hydrogen sulfide contributes to retinal neovascularization in Ischemia-Induced retinopathy",
abstract = "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.",
keywords = "Hydrogen sulfide, Neovascularization, Oxygen-induced retinopathy",
author = "David Gersztenkorn and Ciro Coletta and Shuang Zhu and Yonju Ha and Hua Liu and Hongyan Tie and Jia Zhou and Csaba Szabo and Wenbo Zhang and Massoud Motamedi",
year = "2016",
month = "6",
day = "1",
doi = "10.1167/iovs.15-18555",
language = "English (US)",
volume = "57",
pages = "3002--3009",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "7",

}

TY - JOUR

T1 - Hydrogen sulfide contributes to retinal neovascularization in Ischemia-Induced retinopathy

AU - Gersztenkorn, David

AU - Coletta, Ciro

AU - Zhu, Shuang

AU - Ha, Yonju

AU - Liu, Hua

AU - Tie, Hongyan

AU - Zhou, Jia

AU - Szabo, Csaba

AU - Zhang, Wenbo

AU - Motamedi, Massoud

PY - 2016/6/1

Y1 - 2016/6/1

N2 - 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.

AB - 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.

KW - Hydrogen sulfide

KW - Neovascularization

KW - Oxygen-induced retinopathy

UR - http://www.scopus.com/inward/record.url?scp=84973364238&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84973364238&partnerID=8YFLogxK

U2 - 10.1167/iovs.15-18555

DO - 10.1167/iovs.15-18555

M3 - Article

VL - 57

SP - 3002

EP - 3009

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 7

ER -