Hydrogen Sulfide Contributes to Retinal Neovascularization in Ischemia-Induced Retinopathy.
Hydrogen Sulfide Contributes to Retinal Neovascularization in Ischemia-Induced Retinopathy.
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DOI：
10.1167/iovs.15-18555
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发表时间：
2016-06-01
影响因子：
4.4
通讯作者：
Motamedi M
中科院分区：
文献类型：
--
作者：
Gersztenkorn D;Coletta C;Zhu S;Ha Y;Liu H;Tie H;Zhou J;Szabo C;Zhang W;Motamedi M
硫化氢（H2S）是一种内源性气体信号分子，具有重要的病理生理意义，但其在视网膜新生血管性疾病中的作用尚不清楚。硫化氢通过胱硫醚-β-合酶（CBS）、胱硫醚-γ-裂解酶（CSE）和/或3-巯基丙酮酸硫转移酶（3-MST）从L-半胱氨酸产生。本研究旨在探讨硫化氢在缺血性视网膜病变视网膜新生血管（NV）中的作用。在氧诱导的视网膜病变（OIR）的鼠模型中进行研究。用荧光测定法检测硫化氢。采用免疫印迹和免疫组织化学方法检测H2S产生酶的变化。采用基因缺失和药物抑制的方法研究H2S在视网膜NV中的作用。与室内空气（RA）对照组相比，OIR小鼠视网膜中硫化氢的产生显著增加。在OIR视网膜中，胱硫醚-β-合成酶和CSE显著增加，而3-MST无变化。胱硫醚-β-合成酶在整个神经元视网膜中表达，并在OIR期间在神经元和胶质细胞中上调。胱硫醚-γ-裂解酶也定位于视网膜的多个层。CBS/CSE的药理学抑制或CSE的基因缺失显着降低视网膜NV在OIR。我们的数据表明，H2S生成酶/H2S有助于视网膜NV在缺血诱导的视网膜病变，并建议阻断这一途径可能提供新的治疗方法，用于治疗增殖性视网膜病变。
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.