Topical Use of Angiopoietin-like Protein 2 RNAi-loaded Lipid Nanoparticles Suppresses Corneal Neovascularization.
Topical Use of Angiopoietin-like Protein 2 RNAi-loaded Lipid Nanoparticles Suppresses Corneal Neovascularization.
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DOI：
10.1038/mtna.2016.1
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发表时间：
2016-03-08
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--
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角膜新生血管（CNV）是一种威胁视力的疾病，在包括化学损伤在内的各种炎症环境中都会遇到。我们最近证实血管生成素样蛋白2（ANGPTL 2）是角膜中一种有效的血管生成和促炎因子，我们已经生产了一种单链脯氨酸修饰的短发夹抗ANGPTL 2 RNA干扰分子，该分子携带在脂质纳米颗粒（ANGPTL 2 Li-pshRNA）中用于局部应用。在这项研究中，我们进一步检查了该分子的局部递送和抗ANGPTL 2活性，并发现荧光标记的ANGPTL 2 Li-pshRNA滴眼液可以渗透角膜的所有层，并且在给药后12和24小时，ANGPTL 2 mRNA表达在上皮和基质中均受到显著抑制。我们还检查了ANGPTL 2 Li-pshRNA对小鼠化学损伤模型中CNV的抑制作用，发现与对照组相比，用ANGPTL 2 Li-pshRNA滴眼液处理的角膜中血管生成面积显著减少。总而言之，这些发现表明这种修饰的RNA干扰剂在临床上可以作为局部制剂用于对抗CNV。
Corneal neovascularization (CNV) is a sight-threatening condition that is encountered in various inflammatory settings including chemical injury. We recently confirmed that angiopoietin-like protein 2 (ANGPTL2) is a potent angiogenic and proinflammatory factor in the cornea, and we have produced a single-stranded proline-modified short hairpin anti-ANGPTL2 RNA interference molecule that is carried in a lipid nanoparticle (ANGPTL2 Li-pshRNA) for topical application. In this study, we have further examined the topical delivery and anti-ANGPTL2 activity of this molecule and have found that fluorescence-labeled ANGPTL2 Li-pshRNA eye drops can penetrate all layers of the cornea and that ANGPTL2 mRNA expression was dramatically inhibited in both epithelium and stroma at 12 and 24 hours after administration. We also examined the inhibitory effect of ANGPTL2 Li-pshRNA on CNV in a mouse chemical injury model and found that the area of angiogenesis was significantly decreased in corneas treated with ANGPTL2 Li-pshRNA eye drops compared to controls. Together, these findings indicate that this modified RNA interference agent is clinically viable in a topical formulation for use against CNV.
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影响因子：
2
作者：
Sotozono, C;He, JC;Kinoshita, S
通讯作者：
Kinoshita, S
DOI：
10.3791/51159
发表时间：
2014-04-07
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Anderson C;Zhou Q;Wang S
通讯作者：
Wang S
影响因子：
5.1
作者：
Chang JH;Garg NK;Lunde E;Han KY;Jain S;Azar DT
通讯作者：
Azar DT
影响因子：
5
作者：
Kanda, Atsuhiro;Noda, Kousuke;Ishida, Susumu
通讯作者：
Ishida, Susumu
影响因子：
4.4
作者：
Shimazaki, Hiroki;Hironaka, Kohei;Hara, Hideaki
通讯作者：
Hara, Hideaki