定时局部使用地塞米松滴眼液可改善线粒体功能,预防严重的早产儿视网膜病变

IF 9.2 1区 医学 Q1 PERIPHERAL VASCULAR DISEASE
Hitomi Yagi, Myriam Boeck, Mariya Petrishka-Lozenska, Pia Lundgren, Taku Kasai, Gael Cagnone, Katherine Neilsen, Chaomei Wang, Jeff Lee, Yohei Tomita, Sasha A. Singh, Jean-Sébastien Joyal, Masanori Aikawa, Kazuno Negishi, Zhongjie Fu, Ann Hellström, Lois E.H. Smith
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引用次数: 0

摘要

早产儿视网膜病变(ROP)中的病理性新生血管可导致早产儿视力受损。目前的早产儿视网膜病变治疗方法并不能预防早产儿视网膜病变,只能解决晚期新生血管性视网膜病变,不仅费用昂贵,还可能导致严重的并发症。我们的研究表明,在新生血管形成高峰之前局部滴用0.1%地塞米松眼药水,可预防5名极度早产儿的新生血管形成,并将小鼠氧诱导视网膜病变(OIR)模型的新生血管形成抑制30%。与此相反,在小鼠氧诱导视网膜病变模型中,在任何新生血管形成之前局部使用地塞米松治疗对防止后期新生血管形成的效果有限,而在新生血管形成高峰之后使用地塞米松治疗则有加重病情的趋势,但无统计学意义。最佳时机局部使用地塞米松抑制 OIR 中的新生血管与视网膜线粒体基因表达增加和炎症标志物表达(主要存在于免疫细胞中)减少有关。阻断线粒体 ATP 合成酶可逆转地塞米松对 OIR 新生血管形成的抑制作用。这项研究为局部类固醇在视网膜新生血管中的作用以及二期 ROP 的线粒体功能提供了新的见解,并提出了一种预防严重 ROP 的简单临床方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Timed topical dexamethasone eye drops improve mitochondrial function to prevent severe retinopathy of prematurity

Timed topical dexamethasone eye drops improve mitochondrial function to prevent severe retinopathy of prematurity

Pathological neovascularization in retinopathy of prematurity (ROP) can cause visual impairment in preterm infants. Current ROP treatments which are not preventative and only address late neovascular ROP, are costly and can lead to severe complications. We showed that topical 0.1% dexamethasone eye drops administered prior to peak neovessel formation prevented neovascularization in five extremely preterm infants at high risk for ROP and suppressed neovascularization by 30% in mouse oxygen-induced retinopathy (OIR) modeling ROP. In contrast, in OIR, topical dexamethasone treatment before any neovessel formation had limited efficacy in preventing later neovascularization, while treatment after peak neovessel formation had a non-statistically significant trend to exacerbating disease. Optimally timed topical dexamethasone suppression of neovascularization in OIR was associated with increased retinal mitochondrial gene expression and decreased inflammatory marker expression, predominantly found in immune cells. Blocking mitochondrial ATP synthetase reversed the inhibitory effect of dexamethasone on neovascularization in OIR. This study provides new insights into topical steroid effects in retinal neovascularization and into mitochondrial function in phase II ROP, and suggests a simple clinical approach to prevent severe ROP.

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来源期刊
Angiogenesis
Angiogenesis PERIPHERAL VASCULAR DISEASE-
CiteScore
21.90
自引率
8.20%
发文量
37
审稿时长
6-12 weeks
期刊介绍: Angiogenesis, a renowned international journal, seeks to publish high-quality original articles and reviews on the cellular and molecular mechanisms governing angiogenesis in both normal and pathological conditions. By serving as a primary platform for swift communication within the field of angiogenesis research, this multidisciplinary journal showcases pioneering experimental studies utilizing molecular techniques, in vitro methods, animal models, and clinical investigations into angiogenic diseases. Furthermore, Angiogenesis sheds light on cutting-edge therapeutic strategies for promoting or inhibiting angiogenesis, while also highlighting fresh markers and techniques for disease diagnosis and prognosis.
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