Wet-AMD on a Chip: Modeling Outer Blood-Retinal Barrier In Vitro

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.

On-chip model of wet type age-related macular degeneration (AMD) that causes severe vision loss in the elderly is described. A process that destructs integrity of retinal pigment epithelium by angiogenesis of choroid vessel, a main pathological process of wet-AMD called choroidal neovascularization (CNV), is reconstituted on a microfluidic platform. Inhibitory effect of a therapeutic antiangiogenic compound on CNV is demonstrated.

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