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青光眼患者眼成纤维细胞中线粒体细胞生物能量的证据受损。

Evidence of impaired mitochondrial cellular bioenergetics in ocular fibroblasts derived from glaucoma patients.

机构信息

Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, L69 3BX, United Kingdom; St. Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, L7 8XP, United Kingdom.

Institute of Systems, Molecular and Integrative Biology, Biosciences Building, University of Liverpool, Liverpool, L69 7BE, United Kingdom.

出版信息

Free Radic Biol Med. 2022 Aug 20;189:102-110. doi: 10.1016/j.freeradbiomed.2022.07.009. Epub 2022 Jul 22.

DOI:10.1016/j.freeradbiomed.2022.07.009
PMID:35872337
Abstract

Glaucoma is a progressive optic neuropathy characterized by the neurodegeneration of the retinal ganglion cells (RGCs) resulting in irreversible visual impairment and eventual blindness. RGCs are extremely susceptible to mitochondrial compromise due to their marked bioenergetic requirements and morphology. There is increasing interest in therapies targeting mitochondrial health as a method of preventing visual loss in managing glaucoma. The bioenergetic profile of Tenon's ocular fibroblasts from glaucoma patients and controls was investigated using the Seahorse XF24 analyser. Impaired mitochondrial cellular bioenergetics was detected in glaucomatous ocular fibroblasts including basal respiration, maximal respiration and spare capacity. Spare respiratory capacity levels reflect mitochondrial bio-energetic adaptability in response to pathophysiological stress. Basal oxidative stress was elevated in glaucomatous Tenon's ocular fibroblasts and hydrogen peroxide (HO) induced reactive oxygen species (ROS) simulated the glaucomatous condition in normal Tenon's ocular fibroblasts. This work supports the role of therapeutic interventions to target oxidative stress or provide mitochondrial energetic support in glaucoma.

摘要

青光眼是一种进行性视神经病变,其特征是视网膜神经节细胞(RGCs)的神经退行性变,导致不可逆转的视力损害和最终失明。由于 RGCs 的显著生物能量需求和形态,它们极易受到线粒体功能障碍的影响。人们越来越关注靶向线粒体健康的疗法,作为预防青光眼管理中视力丧失的一种方法。使用 Seahorse XF24 分析仪研究了来自青光眼患者和对照者的 Tenon 眼纤维细胞的生物能量谱。在青光眼眼纤维细胞中检测到受损的线粒体细胞生物能量学,包括基础呼吸、最大呼吸和备用能力。备用呼吸能力水平反映了线粒体生物能量学对病理生理应激的适应性。在青光眼 Tenon 眼纤维细胞中,基础氧化应激升高,过氧化氢(HO)诱导的活性氧(ROS)模拟了正常 Tenon 眼纤维细胞中的青光眼状态。这项工作支持了针对氧化应激或提供线粒体能量支持的治疗干预在青光眼治疗中的作用。

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