Related Experiment Video
Updated: Oct 6, 2025
An Ex Vivo Choroid Sprouting Assay of Ocular Microvascular Angiogenesis
Published on: August 6, 2020
Human immunocompetent choroid-on-chip: a novel tool for studying ocular effects of biological drugs
Madalena Cipriano1,2, Katharina Schlünder1,3, Christopher Probst4
1Institute for Biomedical Engineering, Eberhard Karls University Tübingen, Tübingen, Germany.
Abstract:
Disorders of the eye leading to visual impairment are a major issue that affects millions of people. On the other side ocular toxicities were described for e.g. molecularly targeted therapies in oncology and may hamper their development. Current ocular model systems feature a number of limitations affecting human-relevance and availability. To find new options for pharmacological treatment and assess mechanisms of toxicity, hence, novel complex model systems that are human-relevant and readily available are urgently required. Here, we report the development of a human immunocompetent Choroid-on-Chip (CoC), a human cell-based in vitro model of the choroid layer of the eye integrating melanocytes and microvascular endothelial cells, covered by a layer of retinal pigmented epithelial cells. Immunocompetence is achieved by perfusion of peripheral immune cells. We demonstrate controlled immune cell recruitment into the stromal compartments through a vascular monolayer and in vivo-like cytokine release profiles. To investigate applicability for both efficacy testing of immunosuppressive compounds as well as safety profiling of immunoactivating antibodies, we exposed the CoCs to cyclosporine and tested CD3 bispecific antibodies.
Insights
A new human immunocompetent Choroid-on-Chip model integrates eye cells and immune cells. This advanced in vitro model aids drug development by testing efficacy and toxicity for ocular conditions.
Area of Science:
- Ophthalmology
- Immunology
- Biomedical Engineering
Background:
- Ocular disorders cause widespread visual impairment.
- Ocular toxicities from therapies like targeted cancer treatments hinder drug development.
- Existing ocular models lack human-relevance and availability.
Purpose of the Study:
- To develop a novel, human-relevant, and accessible in vitro model for ocular research.
- To create a complex model system for pharmacological treatment options and toxicity assessments.
- To establish an immunocompetent Choroid-on-Chip model for advanced eye research.
Main Methods:
- Development of a human cell-based Choroid-on-Chip (CoC) model.
- Integration of choroidal melanocytes, microvascular endothelial cells, and retinal pigmented epithelial cells.
- Achieving immunocompetence via peripheral immune cell perfusion and demonstrating controlled immune cell recruitment.
Main Results:
- The CoC model successfully integrated key ocular cell types.
- Controlled immune cell recruitment into the choroidal stroma was achieved.
- In vivo-like cytokine release profiles were observed, and the model responded to cyclosporine and CD3 bispecific antibodies.
Conclusions:
- The developed human immunocompetent Choroid-on-Chip (CoC) represents a significant advancement in ocular modeling.
- This model is suitable for evaluating the efficacy of immunosuppressive drugs and the safety of immunoactivating antibodies.
- The CoC offers a promising platform for future ocular drug discovery and toxicity studies.
