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在兔眼中通过金纳米颗粒进行视网膜下免疫球蛋白G递送。

Subretinal delivery of immunoglobulin G with gold nanoparticles in the rabbit eye.

作者信息

Hayashi Atsushi, Naseri Ayman, Pennesi Mark E, de Juan Eugene

机构信息

Department of Ophthalmology, University of California, San Francisco, CA, USA.

出版信息

Jpn J Ophthalmol. 2009 May;53(3):249-56. doi: 10.1007/s10384-009-0655-x. Epub 2009 May 31.

Abstract

PURPOSE

To examine the feasibility of subretinal delivery of immunoglobulin G (IgG) adsorbed onto gold nanoparticles (GNPs) and its histologic distribution in the rabbit retina after the injection.

METHODS

Goat IgG was adsorbed onto GNPs electrostatically. Goat IgG-adsorbed GNPs or buffer with goat IgG was injected into the subretinal space of rabbit eyes and followed up for 3 months by examination of fundus photographs, immunohistochemistry against goat IgG, and transmission electron microscopy (TEM). Human retinal pigment epithelial cells (ARPE-19 cells) were cultured, and cell proliferation with or without GNPs was assayed.

RESULTS

At 1 week after the subretinal injection of goat IgG-adsorbed GNPs, retinal degeneration was observed in the outer retina, and goat IgG was immunolabeled in the retinal pigment epithelium (RPE) and the photoreceptor cells. TEM showed GNPs located in the outer segments and in the lysosomes in the RPE at 1 month and no apparent cytotoxicity of the RPE. There were no inhibitory effects of GNPs on proliferation of ARPE-19 cells.

CONCLUSIONS

Goat IgG was successfully delivered into photoreceptor cells and RPE using GNPs, though retinal degeneration in the outer retina occurred in this model. This might be an alternative drug delivery method to photoreceptors and RPE.

摘要

目的

研究吸附于金纳米颗粒(GNP)上的免疫球蛋白G(IgG)经视网膜下给药的可行性及其注射后在兔视网膜中的组织学分布。

方法

将山羊IgG静电吸附于GNP上。将吸附有山羊IgG的GNP或含山羊IgG的缓冲液注入兔眼视网膜下间隙,并通过眼底照相、抗山羊IgG免疫组织化学和透射电子显微镜(TEM)检查进行3个月的随访。培养人视网膜色素上皮细胞(ARPE - 19细胞),检测有无GNP时的细胞增殖情况。

结果

视网膜下注射吸附有山羊IgG的GNP后1周,在外层视网膜观察到视网膜变性,在视网膜色素上皮(RPE)和光感受器细胞中检测到山羊IgG免疫标记。TEM显示1个月时GNP位于RPE的外节和溶酶体中,且RPE无明显细胞毒性。GNP对ARPE - 19细胞的增殖无抑制作用。

结论

使用GNP成功将山羊IgG递送至光感受器细胞和RPE,尽管在此模型中外层视网膜发生了视网膜变性。这可能是一种向光感受器和RPE给药的替代方法。

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