Abstract
AbstractDisorders 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.
Publisher
Springer Science and Business Media LLC
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
Reference59 articles.
1. Marx, U. et al. Biology-inspired microphysiological systems to advance medicines for patient benefit and animal welfare. ALTEX 37, 365–394 (2020).
2. Franzen, N. et al. Impact of organ-on-a-chip technology on pharmaceutical R&D costs. Drug Discov. Today 24, 1720–1724 (2019).
3. Bourne, R. R. A. et al. Magnitude, temporal trends, and projections of the global prevalence of blindness and distance and near vision impairment: a systematic review and meta-analysis. Lancet Glob. Health 5, e888–e897 (2017).
4. Renouf, D. J., Velazquez-Martin, J. P., Simpson, R., Siu, L. L. & Bedard, P. L. Ocular toxicity of targeted therapies. J. Clin. Oncol. 30, 3277–3286 (2012).
5. Liu, X. et al. Clinical diagnosis and treatment recommendations for ocular toxicities of targeted therapy and immune checkpoint inhibitor therapy. Thorac. Cancer 11, 810–818 (2020).
Cited by
13 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献