Human Retina-on-a-Chip: Merging Organoid and Organ-on-a-Chip Technology to Generate Complex Multi-Layer Tissue Models
| Autor: | Stefan Liebau, Peter Loskill, Christopher Probst, Julia Rogal, Nian Shen, Jasmin Haderspeck, Sylvia Bolz, Marius Ueffing, Kevin Achberger, Katja Schenke-Layland, Marina Nikolova, Johanna Chuchuy, Virginia Cora, Wadood Haq, Lena Antkowiak |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Retina Retinal pigment epithelium genetic structures Retinal Biology medicine.disease Organ-on-a-chip Embryonic stem cell 3. Good health Stargardt disease 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine.anatomical_structure Drug development chemistry Retinitis pigmentosa 030221 ophthalmology & optometry medicine Neuroscience 030304 developmental biology |
| DOI: | 10.1101/552158 |
| Popis: | The devastating effects and incurable nature of hereditary and sporadic retinal diseases such as Stargardt disease, age-related macular degeneration or retinitis pigmentosa urgently require the development of new therapeutic strategies. Additionally, the prevalence of retinal toxicities is becoming more and more an issue of novel targeted therapeutic agents. To date, (ophthalmologic) drug development largely relies on animal models. Inadequate translatability of results from animal models to humans, however, limits advances in drug development and discovery. Hence, the establishment of more relevant human tissue-based in vitro models is of upmost importance. The discovery of self-forming retinal organoids (ROs) derived from human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs) is a promising approach to model the complex stratified retinal tissue. Yet, ROs lack vascularization and cannot recapitulate the important physiological interactions of matured photoreceptors and the retinal pigment epithelium (RPE). In this study, we present the retina-on-a-chip (RoC), a novel microphysiological model of the human retina integrating more than seven different essential retinal cell types derived from hiPSCs in a vasculature-like perfusion and enabling, for the first time, the recapitulation of the interaction of mature photoreceptor segments with RPE in vitro. We show that this interaction enhances the formation of outer segment like-structures and the establishment of in vivo-like physiological processes such as outer segment phagocytosis and calcium dynamics. In addition, we demonstrate the applicability of the RoC for drug testing, by reproducing the retinopathic side effects of the anti-malaria drug chloroquine and the antibiotic gentamicin. The developed hiPSC-based RoC has the potential to promote drug development and provide new insights into the underlying pathology of retinal diseases. |
| Databáze: | OpenAIRE |
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