PDF(Pubmed)
Abstract：
UNASSIGNED: The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) stimulator of interferon gene (STING) pathway is a crucial cascade in the inflammatory response initiated by the recognition of cytosolic double-stranded DNA (dsDNA). The aim of this study was to evaluate the effect of STING inhibitor in murine choroidal neovascularization (CNV).
UNASSIGNED: To investigate whether the cGAS-STING pathway is activated during CNV, CNV was induced using laser photocoagulation in male C57BL/6J mice. The expression of change of cGAS and STING during CNV development was confirmed by Western-blotting. H-151, a potent STING palmitoylation antagonist, was used as a STING inhibitor. H-151 was administered intravitreally immediately after laser induction. To confirm the role of the cGAS-STING pathway in CNV formation, we evaluated CNV size and performed fundus fluorescein angiography.
UNASSIGNED: The expression levels of cGAS and STING were significantly upregulated in the RPE-choroid complex after CNV induction, and dsDNA merged with cGAS was observed in CNV lesions. Intravitreal administration of H-151 suppressed CNV development and fluorescent leakage from neovessels. In CNV lesions, the high expression of STING and cGAS was observed in infiltrating F4/80+ macrophages. H-151 administration attenuated downstream signals of the cGAS-STING pathway, including the phosphorylation of nuclear factor-κB, and downregulated the expression of interleukin 1β.
UNASSIGNED: These findings support that the inhibition of cGAS-STING pathway treats abnormal ocular angiogenesis.
UNASSIGNED: To investigate whether the cGAS-STING pathway is activated during CNV, CNV was induced using laser photocoagulation in male C57BL/6J mice. The expression of change of cGAS and STING during CNV development was confirmed by Western-blotting. H-151, a potent STING palmitoylation antagonist, was used as a STING inhibitor. H-151 was administered intravitreally immediately after laser induction. To confirm the role of the cGAS-STING pathway in CNV formation, we evaluated CNV size and performed fundus fluorescein angiography.
UNASSIGNED: The expression levels of cGAS and STING were significantly upregulated in the RPE-choroid complex after CNV induction, and dsDNA merged with cGAS was observed in CNV lesions. Intravitreal administration of H-151 suppressed CNV development and fluorescent leakage from neovessels. In CNV lesions, the high expression of STING and cGAS was observed in infiltrating F4/80+ macrophages. H-151 administration attenuated downstream signals of the cGAS-STING pathway, including the phosphorylation of nuclear factor-κB, and downregulated the expression of interleukin 1β.
UNASSIGNED: These findings support that the inhibition of cGAS-STING pathway treats abnormal ocular angiogenesis.
摘要：
干扰素基因(STING)途径的环磷酸鸟苷-磷酸腺苷合成酶(cGAS)刺激物是由细胞溶质双链DNA(dsDNA)的识别引发的炎症反应中的关键级联。这项研究的目的是评估STING抑制剂在鼠脉络膜新生血管形成（CNV）中的作用。
■为了研究cGAS-STING通路在CNV期间是否被激活，在雄性C57BL/6J小鼠中使用激光光凝法诱导CNV。通过Western印迹证实了cGAS和STING在CNV发育过程中的表达变化。H-151，一种有效的STING棕榈酰化拮抗剂，用作STING抑制剂。在激光诱导后立即玻璃体内施用H-151。为了证实cGAS-STING途径在CNV形成中的作用，我们评估了CNV大小并进行了荧光素眼底血管造影.
■在CNV诱导后RPE-脉络膜复合体中cGAS和STING的表达水平显著上调,在CNV病变中观察到dsDNA与cGAS合并。玻璃体内施用H-151抑制了CNV的发展和新血管的荧光渗漏。在CNV病变中，在浸润的F4/80+巨噬细胞中观察到STING和cGAS的高表达。H-151给药减弱了cGAS-STING途径的下游信号，包括核因子-κB的磷酸化,并下调白细胞介素1β的表达。
■这些发现支持cGAS-STING途径的抑制治疗异常的眼部血管生成。
■为了研究cGAS-STING通路在CNV期间是否被激活，在雄性C57BL/6J小鼠中使用激光光凝法诱导CNV。通过Western印迹证实了cGAS和STING在CNV发育过程中的表达变化。H-151，一种有效的STING棕榈酰化拮抗剂，用作STING抑制剂。在激光诱导后立即玻璃体内施用H-151。为了证实cGAS-STING途径在CNV形成中的作用，我们评估了CNV大小并进行了荧光素眼底血管造影.
■在CNV诱导后RPE-脉络膜复合体中cGAS和STING的表达水平显著上调,在CNV病变中观察到dsDNA与cGAS合并。玻璃体内施用H-151抑制了CNV的发展和新血管的荧光渗漏。在CNV病变中，在浸润的F4/80+巨噬细胞中观察到STING和cGAS的高表达。H-151给药减弱了cGAS-STING途径的下游信号，包括核因子-κB的磷酸化,并下调白细胞介素1β的表达。
■这些发现支持cGAS-STING途径的抑制治疗异常的眼部血管生成。
