Yameng Liu , Qianwen Bu , Die Hu , Chen Chen , Jiaxi Zhu , Qingjun Zhou , Zongyi Li , Xiaojing Pan
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引用次数: 0
摘要
青光眼的特点是由于小梁网(TM)功能障碍导致眼内压(IOP)病理性升高,这是造成不可逆视力损失的主要原因。青光眼目前尚无有效的治疗策略。线粒体功能在调节小梁网内的眼压方面起着至关重要的作用。在这项研究中,用地塞米松处理的原发性 TM 细胞模拟了青光眼的变化,显示出细胞骨架异常、细胞外基质表达增加以及线粒体融合和裂变动力学紊乱。此外,与正常 TM 细胞 iHTM 相比,青光眼 TM 细胞系 GTM3 的线粒体膜电位和吞噬功能受损,氧化呼吸水平下降。从机理上讲,在 GTM3 中观察到较低的 NAD + 水平,这可能与与 NAD + 消耗有关的关键酶 CD38 和 PARP1 的表达增加有关。补充 NAD + 可恢复 GTM3 细胞的线粒体功能和细胞活力。因此,我们认为青光眼 TM 细胞线粒体功能异常可能是由于依赖于 CD38 和 PARP1 的 NAD + 消耗增加所致,而补充 NAD + 可以有效改善线粒体功能和 TM 功能,为青光眼治疗提供了一种新的替代方法。
NAD+ supplementation improves mitochondrial functions and normalizes glaucomatous trabecular meshwork features
Glaucoma is characterized by pathological elevation of intraocular pressure (IOP) due to dysfunctional trabecular meshwork (TM), which is the primary cause of irreversible vision loss. There are currently no effective treatment strategies for glaucoma. Mitochondrial function plays a crucial role in regulating IOP within the TM. In this study, primary TM cells treated with dexamethasone were used to simulate glaucomatous changes, showing abnormal cellular cytoskeleton, increased expression of extracellular matrix, and disrupted mitochondrial fusion and fission dynamics. Furthermore, glaucomatous TM cell line GTM3 exhibited impaired mitochondrial membrane potential and phagocytic function, accompanied by decreased oxidative respiratory levels as compared to normal TM cells iHTM. Mechanistically, lower NAD + levels in GTM3, possibly associated with increased expression of key enzymes CD38 and PARP1 related to NAD + consumption, were observed. Supplementation of NAD + restored mitochondrial function and cellular viability in GTM3 cells. Therefore, we propose that the aberrant mitochondrial function in glaucomatous TM cells may be attributed to increased NAD + consumption dependent on CD38 and PARP1, and NAD + supplementation could effectively ameliorate mitochondrial function and improve TM function, providing a novel alternative approach for glaucoma treatment.
期刊介绍:
Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.