转甲状腺素
淀粉样变性
基因沉默
小干扰RNA
结合
医学
化学
全身给药
房水
药理学
分子生物学
眼科
病理
基因
生物
转染
生物化学
体内
遗传学
数学分析
数学
作者
Tetsu Watanabe,Yuji Takihara,Hirofumi Jono,Tomokazu Fujimoto,Masayoshi Tasaki,Aito Isoguchi,Yui Urahashi,Takefumi Shimoda,Eri Takahashi,Yukio Ando,Shinji Ueno,Mitsuharu Ueda,Toshihiro Inoue
标识
DOI:10.1016/j.bbrc.2023.149397
摘要
The first small interfering RNA (siRNA) therapeutic received approval for hereditary transthyretin (ATTRv) amyloidosis, and the patients' lifespan extension by specific inhibition of hepatic synthesis of transthyretin (TTR) is expected. However, ocular amyloidosis in these patients has been a crucial issue. This study aims to evaluate the efficacy and safety of intravitreal TTR siRNA conjugate injection into rabbit eyes. Rabbit (r) TTR siRNA is a screened TTR siRNA conjugate from 53 candidates. The intraocular pressure (IOP) immediately after injection was high despite the 65.9 % decrease of aqueous humor TTR protein levels in the rTTR siRNA group compared with those in the Control siRNA group 2 weeks after the 50 μL siRNA injection. The IOP spike was milder after the 30 μL siRNA injection, and aqueous humor TTR levels decreased by ∼50 % in the rTTR siRNA group, which is consistent with the mRNA levels in the retina. The parameters of dark-adapted, light-adapted, and light-adapted 30 Hz electroretinogram and the thickness of each retinal layer in histological analysis demonstrated no significant differences between the groups. In conclusion, we developed TTR siRNA conjugates for rabbit eyes, and the results indicate that intravitreal TTR siRNA conjugate injection could be a therapeutic option for ocular amyloidosis caused by ATTRv amyloidosis.
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