Abstract：
UNASSIGNED: Glucocorticoid-induced glaucoma (GIG) is a prevalent complication associated with glucocorticoids (GCs), resulting in irreversible blindness. GIG is characterized by the abnormal deposition of extracellular matrix (ECM) in the trabecular meshwork (TM), elevation of intraocular pressure (IOP), and loss of retinal ganglion cells (RGCs). The objective of this study is to investigate the effects of nicotinamide riboside (NR) on TM in GIG.
UNASSIGNED: Primary human TM cells (pHTMs) and C57BL/6J mice responsive to GCs were utilized to establish in vitro and in vivo GIG models, respectively. The study assessed the expression of ECM-related proteins in TM and the functions of pHTMs to reflect the effects of NR. Mitochondrial morphology and function were also examined in the GIG cell model. GIG progression was monitored through IOP, RGCs, and mitochondrial morphology. Intracellular nicotinamide adenine dinucleotide (NAD+) levels of pHTMs were enzymatically assayed.
UNASSIGNED: NR significantly prevented the expression of ECM-related proteins and alleviated dysfunction in pHTMs after dexamethasone treatment. Importantly, NR protected damaged ATP synthesis, preventing overexpression of mitochondrial reactive oxygen species (ROS), and also protect against decreased mitochondrial membrane potential induced by GCs in vitro. In the GIG mouse model, NR partially prevented the elevation of IOP and the loss of RGCs. Furthermore, NR effectively suppressed the excessive expression of ECM-associated proteins and mitigated mitochondrial damage in vivo.
UNASSIGNED: Based on the results, NR effectively enhances intracellular levels of NAD+, thereby mitigating abnormal ECM deposition and TM dysfunction in GIG by attenuating mitochondrial damage induced by GCs. Thus, NR has promising potential as a therapeutic candidate for GIG treatment.
UNASSIGNED: Primary human TM cells (pHTMs) and C57BL/6J mice responsive to GCs were utilized to establish in vitro and in vivo GIG models, respectively. The study assessed the expression of ECM-related proteins in TM and the functions of pHTMs to reflect the effects of NR. Mitochondrial morphology and function were also examined in the GIG cell model. GIG progression was monitored through IOP, RGCs, and mitochondrial morphology. Intracellular nicotinamide adenine dinucleotide (NAD+) levels of pHTMs were enzymatically assayed.
UNASSIGNED: NR significantly prevented the expression of ECM-related proteins and alleviated dysfunction in pHTMs after dexamethasone treatment. Importantly, NR protected damaged ATP synthesis, preventing overexpression of mitochondrial reactive oxygen species (ROS), and also protect against decreased mitochondrial membrane potential induced by GCs in vitro. In the GIG mouse model, NR partially prevented the elevation of IOP and the loss of RGCs. Furthermore, NR effectively suppressed the excessive expression of ECM-associated proteins and mitigated mitochondrial damage in vivo.
UNASSIGNED: Based on the results, NR effectively enhances intracellular levels of NAD+, thereby mitigating abnormal ECM deposition and TM dysfunction in GIG by attenuating mitochondrial damage induced by GCs. Thus, NR has promising potential as a therapeutic candidate for GIG treatment.
摘要：
■糖皮质激素诱导的青光眼（GIG）是与糖皮质激素（GC）相关的常见并发症，导致不可逆转的失明。GIG的特征是细胞外基质（ECM）在小梁网（TM）中的异常沉积，眼内压（IOP）升高，和视网膜神经节细胞（RGC）的损失。本研究的目的是研究烟酰胺核苷（NR）对GIG中TM的影响。
■利用对GC有反应的原代人TM细胞（pHTMs）和C57BL/6J小鼠建立体外和体内GIG模型，分别。该研究评估了TM中ECM相关蛋白的表达以及pHTMs的功能，以反映NR的作用。还在GIG细胞模型中检查了线粒体形态和功能。通过IOP监测GIG进展，RGC,和线粒体形态。酶促测定pHTM的细胞内烟酰胺腺嘌呤二核苷酸（NAD）水平。
■NR在地塞米松治疗后显著阻止ECM相关蛋白的表达并减轻pHTM的功能障碍。重要的是,NR保护受损的ATP合成，防止线粒体活性氧（ROS）的过度表达，并且还可以防止体外GCs诱导的线粒体膜电位降低。在GIG小鼠模型中,NR部分防止了IOP的升高和RGC的损失。此外，NR有效抑制ECM相关蛋白的过度表达，减轻体内线粒体损伤。
■根据结果，NR有效增强细胞内NAD+水平，从而通过减弱由GC诱导的线粒体损伤来减轻GIG中的异常ECM沉积和TM功能障碍。因此，NR作为GIG治疗的治疗候选物具有有希望的潜力。
■利用对GC有反应的原代人TM细胞（pHTMs）和C57BL/6J小鼠建立体外和体内GIG模型，分别。该研究评估了TM中ECM相关蛋白的表达以及pHTMs的功能，以反映NR的作用。还在GIG细胞模型中检查了线粒体形态和功能。通过IOP监测GIG进展，RGC,和线粒体形态。酶促测定pHTM的细胞内烟酰胺腺嘌呤二核苷酸（NAD）水平。
■NR在地塞米松治疗后显著阻止ECM相关蛋白的表达并减轻pHTM的功能障碍。重要的是,NR保护受损的ATP合成，防止线粒体活性氧（ROS）的过度表达，并且还可以防止体外GCs诱导的线粒体膜电位降低。在GIG小鼠模型中,NR部分防止了IOP的升高和RGC的损失。此外，NR有效抑制ECM相关蛋白的过度表达，减轻体内线粒体损伤。
■根据结果，NR有效增强细胞内NAD+水平，从而通过减弱由GC诱导的线粒体损伤来减轻GIG中的异常ECM沉积和TM功能障碍。因此，NR作为GIG治疗的治疗候选物具有有希望的潜力。
