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一种可通过光激活的氧化捐赠剂,用于针对性眼球治疗,具有实时监控能力

Jiamin Liu¹, Yankun Lu², Yi Tian¹

¹Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, NHC Key Laboratory of Myopia and Related Eye Diseases, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, 200031, China.

Advanced healthcare materials

|March 19, 2025

概括

一种新型的光激活氧化 (NO) 供体RhNO-Ab有效降低眼内压力 (IOP) 在青光眼模型中. 这种可见光触发的治疗也增强了NO的释放,并允许实时监测潜在的POAG治疗.

科学领域:

眼科医生眼科眼科
生物医学工程生物医学工程
药理学药理学是指药理学的学科.

背景情况:

初级开角青光眼 (POAG) 是最常见的青光眼形式,其特征是眼内压力升高 (IOP).
氧化 (NO) 捐赠者对POAG具有治疗潜力,但需要有针对性和刺激响应的释放机制.
现有的NO捐赠体缺乏由眼部相关刺激触发的选择性释放,限制了它们的临床应用.

研究的目的:

推出RhNO-Ab,一种可见光激活的新型NO捐赠器和光探针用于POAG治疗.
评估RhNO-Ab在降低IOP及其在临床前模型中的作用机制的疗效.
评估RhNO-Ab在实时监测NO释放和治疗输送方面的潜力.

主要方法:

RhNO-Ab的合成和表征,包括在可见光照射后NO释放和光恢复的体外研究.
免疫光成像以评估RhNO-Ab的组织向与抗体修饰.
在RhNO-Ab给药和光处理后,在NOS3 KO小鼠体内IOP测量.
在Schlemm通道内皮细胞中评估超内皮电阻 (TEER).
在眼睛组织中分析可溶性酸环酶 (sGC) mRNA和蛋白质表达.

主要成果:

对RhNO-Ab的可见光照射引发了快速的NO释放和光恢复.
在NOS3 KO小鼠中,RhNO-Ab与光显著降低了IOP.
RhNO-Ab治疗减少了施莱姆运河内皮细胞中的TEER,并提高了sGC表达的调节.
抗体修饰增强了RhNO-Ab的传递,以准眼睛组织.

结论:

RhNO-Ab是一种有前途的可见光可激活NO捐赠器和光探针,用于POAG治疗.
从RhNO-Ab中释放的光触发的NO有效降低了内脏压力,并调节了玻璃眼的关键途径.
RhNO-Ab为POAG治疗提供了一种新的策略,附带实时监测的额外好处.

关键词:

没有任何的捐赠者.眼内压力眼内压力主要的开角绿眼 glaucoma 的情况.罗达胺是一种胺.可见光-可启动的可见光.

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