Nanoprotection Against Retinal Pigment Epithelium Degeneration via Ferroptosis Inhibition,Small Methods

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Nanoprotection Against Retinal Pigment Epithelium Degeneration via Ferroptosis Inhibition
Small Methods ( IF 10.7 ) Pub Date : 2021-11-10 , DOI: 10.1002/smtd.202100848
Zhimin Tang _{1,

2} , Minfeng Huo ₃ , Yahan Ju _{1,

2} , Xiaochan Dai _{1,

2} , Ni Ni _{1,

2} , Yan Liu _{1,

2} , Huiqin Gao _{1,

2} , Dandan Zhang _{1,

2} , Hao Sun _{1,

2} , Xianqun Fan _{1,

2} , Yu Chen ₄ , Ping Gu _{1,

2}

Affiliation

Lethal oxidative stress and ferrous ion accumulation-mediated degeneration/death in retinal pigment epithelium (RPE) exert an indispensable impact on retinal degenerative diseases with irreversible visual impairment, especially in age-related macular degeneration (AMD), but corresponding pathogenesis-oriented medical intervention remains controversial. In this study, the potent iron-binding nanoscale Prussian blue analogue KCa[Fe^III(CN)₆] (CaPB) with high biocompatibility is designed to inhibit RPE death and subsequently photoreceptor cell degeneration. In mice, CaPB effectively prevents RPE degeneration and ultimately fulfills superior therapeutic outcomes upon a single intravitreal injection: significant rescue of retinal structures and visual function. Through high-throughput RNA sequencing and sophisticated biochemistry evaluations, the findings initially unveil that CaPB nanoparticles protect against RPE degradation by inhibiting ferroptotic cell fate. Together with the facile, large-scale preparations and in vivo biosafety, it is believed that the synthesized CaPB therapeutic nanoparticles are promising for future clinical treatment of diverse retinal diseases involving pathological iron-dependent ferroptosis, including AMD.

中文翻译：

通过抑制铁死亡对视网膜色素上皮变性的纳米保护

致命的氧化应激和亚铁离子积累介导的视网膜色素上皮 (RPE) 变性/死亡对具有不可逆视力障碍的视网膜退行性疾病产生不可或缺的影响，特别是在年龄相关性黄斑变性 (AMD) 中，但相应的以发病机制为导向的医疗干预仍有争议。在这项研究中，强效铁结合纳米普鲁士蓝类似物 KCa[Fe ^III (CN) ₆] (CaPB) 具有高生物相容性，旨在抑制 RPE 死亡和随后的感光细胞变性。在小鼠中，CaPB 可有效防止 RPE 变性，并最终通过单次玻璃体内注射实现卓越的治疗效果：显着挽救视网膜结构和视觉功能。通过高通量 RNA 测序和复杂的生物化学评估，研究结果初步揭示了 CaPB 纳米颗粒通过抑制铁死亡细胞的命运来防止 RPE 降解。再加上简便、大规模的制备和体内生物安全性，相信合成的 CaPB 治疗性纳米颗粒有望用于未来临床治疗各种涉及病理性铁依赖性铁死亡的视网膜疾病，包括 AMD。

更新日期：2021-12-14

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