Wet-AMD on a Chip: Modeling Outer Blood-Retinal Barrier In Vitro
Wet-AMD on a Chip: Modeling Outer Blood-Retinal Barrier In Vitro
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DOI：
10.1002/adhm.201700028
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发表时间：
2018-01-24
影响因子：
10
通讯作者：
Kim, Jeong Hun
中科院分区：
文献类型：
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作者：
Chung, Minhwan;Lee, Somin;Kim, Jeong Hun
构成外血视网膜屏障（oBRB）的视网膜色素上皮（RPE）-脉络膜复合体中的脉络膜新生血管（CNV）是多种眼科疾病的关键病理步骤，可导致失明，例如湿型年龄相关性黄斑变性。目前使用培养皿或transwell的体外实验模型无法研究CNV形态发生。在这里，描述了一种独特的器官型芯片眼睛模型，该模型在体外模拟 RPE-脉络膜复合体。该模型由 RPE 单层和相邻的可灌注血管网络组成，支持 oBRB 的屏障功能。 RPE-脉络膜复合体的完整屏障功能被重建，同时保持重要的结构特征。此外，该模型可以成功模拟 CNV 的发病机制，特别是在形态发生方面，即从预先存在的脉络膜血管中穿透血管生成芽，导致 RPE 单层破裂。病理性血管生成的缓解可以用贝伐单抗（一种用于 CNV 治疗的临床药物）来模拟。据信，该模型可与动物模型一起用于帮助开发先进的体外眼药评价。
Choroidal neovascularization (CNV) in the retinal pigment epithelium (RPE)-choroid complex constituting outer blood retinal barrier (oBRB) is a critical pathological step in various ophthalmic diseases, which results in blindness, such as wet type age-related macula degeneration. Current in vitro experimental models using petri dishes or transwell are unable to study CNV morphogenesis. Here, a unique organotypic eye-on-a-chip model is described that mimics the RPE-choroid complex in vitro. This model consists of an RPE monolayer and adjacent perfusable blood vessel network, which is supporting barrier function of oBRB. The intact barrier function of the RPE-choroid complex is reconstituted while maintaining important structural features. Further, this model can successfully mimic the pathogenesis of CNV especially in terms of morphogenesis, which is penetrating angiogenic sprouts from pre-existing choroidal vessels that result in breakdown of RPE monolayer. The alleviation of the pathological angiogenesis can be modeled with bevacizumab, a clinical drug for CNV treatment. It is believed that this model can be used to aid in the development of advanced in vitro eye drug evaluation in conjunction with animal models.