Incidence ofglaucoma, a severe disease leading to irreversible loss of vision, is increasing with global aging populations. Lowering intraocular pressure (IOP) is the only proven treatment method for glaucoma. Nitric oxide (NO) is an emerging material targeting the conventional outflow pathway by relaxing the trabecular meshwork (TM). However, there is little understanding on the NO level effective in IOP lowering without toxicity. Here, we report a novel long-term NO-releasing polydiazeniumdiolate (NOP) that enables lowering IOP via the conventional outflow pathway. NOP is composed of carbon-bound polydiazeniumdiolate, a stable NO donor moiety. NO release was monitored with accurate parameters by real-time detection of gas and analysis of the accumulated release profile. Based on the NO release information, the selected safe level of NOP exhibited effective TM relaxation and a potential IOP lowering effect in vivo without side effects. This work provides new insights into nitric oxide release behavior that should be considered for glaucoma treatment.

中文翻译：

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用于青光眼治疗的持续提供一氧化氮的小分子和精确释放行为的研究。

随着全球人口老龄化，青光眼（一种导致不可逆视力丧失的严重疾病）的发病率正在增加。降低眼压（IOP）是青光眼唯一有效的治疗方法。一氧化氮（NO）是通过松弛小梁网（TM）靶向常规流出途径的新兴材料。但是，对于有效降低眼压而无毒性的NO水平知之甚少。在这里，我们报告了一种新型的长期释放NO的聚二氮杂二氮杂酸酯（NOP），它能够通过常规的流出途径降低IOP。NOP由碳键合的聚二氮杂二醇酯（一种稳定的NO供体部分）组成。通过实时检测气体并分析累积的释放曲线，以精确的参数监控NO的释放。根据NO释放信息，选定的安全水平的NOP在体内显示出有效的TM松弛和潜在的IOP降低效果，而没有副作用。这项工作为青光眼治疗应考虑的一氧化氮释放行为提供了新的见解。