Merging organoid and organ-on-a-chip technology to generate complex multi-layer tissue models in a human retina-on-a-chip platform.
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, a high prevalence of retinal toxicities is becoming more and more an issue of novel targeted therapeutic agents. Ophthalmologic drug development, to date, largely relies on animal models, which often do not provide results that are translatable to human patients. Hence, the establishment of sophisticated 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. It provides vasculature-like perfusion and enables, 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.
Pubmed ID: 31451149 RIS Download
Additional research tools detected in this publication
Antibodies used in this publication
- Chx10 (N-18) (RRID:AB_2216006)
- Rabbit Anti-Opsin, Blue , Unconjugated (RRID:AB_177457)
- Rabbit Anti-ZO-1 PAD Z-R1 Polyclonal Antibody, Unconjugated (RRID:AB_138452)
- Mouse Anti-RPE65 Monoclonal Antibody, Unconjugated, Clone 401.8B11.3D9 (RRID:AB_1566691)
- rhodopsin (1D4) (RRID:AB_785511)
- Rabbit Anti-Pax-6 Polyclonal Antibody, Unconjugated (RRID:AB_291612)
- PKC alpha (C-20) (RRID:AB_2168668)
- Melanoma antibody [HMB45] (RRID:AB_306146)
- Mouse Anti-Human LAMP-2 (H4B4) Monoclonal, Unconjugated, Clone H4b4 (RRID:AB_626858)
- EEA1 Monoclonal Antibody (1G11), eBioscience (RRID:AB_2572928)
- Ezrin Antibody (RRID:AB_2100309)
- CRALBP antibody [B2] (RRID:AB_2269474)
- Brn-3b (H-18) (RRID:AB_2167523)
- AP-2alpha (3B5) (RRID:AB_667767)
- Arrestin-C (I-17) (RRID:AB_2060084)
- Donkey anti-Rabbit IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 647 (RRID:AB_2536183)
- Donkey anti-Rabbit IgG (H+L) ReadyProbes Secondary Antibody, Alexa Fluor™ 488 (RRID:AB_2556546)
- Donkey anti-Rabbit IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 568 (RRID:AB_2534017)
- Donkey Anti-Goat IgG (H+L) Antibody, Alexa Fluor ?? 568 Conjugated (RRID:AB_142581)
- Donkey Anti-Mouse IgG (H+L) Polyclonal Antibody, Alexa Fluor ?? 647 Conjugated (RRID:AB_162542)
- Donkey Anti-Goat IgG (H+L) Antibody, Alexa Fluor 488 Conjugated (RRID:AB_2534102)
- Donkey Anti-Goat IgG (H+L) Antibody, Alexa Fluor ?? 647 Conjugated (RRID:AB_141844)
- Donkey anti-Mouse IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 568 (RRID:AB_2534013)
- Donkey anti-Mouse IgG (H+L) ReadyProbes Secondary Antibody, Alexa Fluor™ 488 (RRID:AB_2556542)
Associated grants
NonePublication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This is a list of tools and resources that we have found mentioned in this publication.
Covance (tool)
RRID:SCR_001224
A contract research organization providing drug development and animal testing services. Under the name Covance Research Products Inc., based in Denver, Pennsylvania, the company also deals in the import, breeding and sale of laboratory animals. It breeds dogs, rabbits, guinea pigs, non-human primates, and pigs, and runs the largest non-human primate laboratory in Germany. (Wikipedia)
View all literature mentionsAbcam (tool)
RRID:SCR_012931
A commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.
View all literature mentionsRabbit Anti-Opsin, Blue , Unconjugated (antibody)
RRID:AB_177457
This unknown targets Opsin, Blue
View all literature mentionsRabbit Anti-ZO-1 PAD Z-R1 Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_138452
This polyclonal targets ZO-1
View all literature mentionsMouse Anti-RPE65 Monoclonal Antibody, Unconjugated, Clone 401.8B11.3D9 (antibody)
RRID:AB_1566691
This monoclonal targets RPE65
View all literature mentionsrhodopsin (1D4) (antibody)
RRID:AB_785511
This monoclonal targets rhodopsin (1D4)
View all literature mentionsRabbit Anti-Pax-6 Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_291612
This polyclonal targets Pax-6
View all literature mentionsPKC alpha (C-20) (antibody)
RRID:AB_2168668
This polyclonal targets PRKCA, PRKCG, PRKCB
View all literature mentionsMelanoma antibody [HMB45] (antibody)
RRID:AB_306146
This monoclonal targets Melanoma
View all literature mentionsMouse Anti-Human LAMP-2 (H4B4) Monoclonal, Unconjugated, Clone H4b4 (antibody)
RRID:AB_626858
This monoclonal targets Human LAMP2
View all literature mentionsEEA1 Monoclonal Antibody (1G11), eBioscience (antibody)
RRID:AB_2572928
This monoclonal targets EEA1
View all literature mentionsCRALBP antibody [B2] (antibody)
RRID:AB_2269474
This monoclonal targets Rlbp1
View all literature mentionsBrn-3b (H-18) (antibody)
RRID:AB_2167523
This polyclonal targets Brn-3b (H-18)
View all literature mentionsAP-2alpha (3B5) (antibody)
RRID:AB_667767
This monoclonal targets TFAP2A
View all literature mentionsArrestin-C (I-17) (antibody)
RRID:AB_2060084
This polyclonal targets Arrestin-C (I-17)
View all literature mentionsDonkey anti-Rabbit IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 647 (antibody)
RRID:AB_2536183
This polyclonal secondary targets IgG (H+L)
View all literature mentionsDonkey anti-Rabbit IgG (H+L) ReadyProbes Secondary Antibody, Alexa Fluor™ 488 (antibody)
RRID:AB_2556546
This polyclonal secondary targets IgG (H+L)
View all literature mentionsDonkey anti-Rabbit IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 568 (antibody)
RRID:AB_2534017
This polyclonal secondary targets IgG (H+L)
View all literature mentionsDonkey Anti-Goat IgG (H+L) Antibody, Alexa Fluor ?? 568 Conjugated (antibody)
RRID:AB_142581
This unknown targets Goat IgG (H+L)
View all literature mentionsDonkey Anti-Mouse IgG (H+L) Polyclonal Antibody, Alexa Fluor ?? 647 Conjugated (antibody)
RRID:AB_162542
This polyclonal targets Mouse IgG (H+L)
View all literature mentionsDonkey Anti-Goat IgG (H+L) Antibody, Alexa Fluor 488 Conjugated (antibody)
RRID:AB_2534102
This unknown targets IgG (H+L)
View all literature mentionsDonkey Anti-Goat IgG (H+L) Antibody, Alexa Fluor ?? 647 Conjugated (antibody)
RRID:AB_141844
This unknown targets Goat IgG (H+L)
View all literature mentionsDonkey anti-Mouse IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 568 (antibody)
RRID:AB_2534013
This polyclonal secondary targets IgG (H+L)
View all literature mentionsDonkey anti-Mouse IgG (H+L) ReadyProbes Secondary Antibody, Alexa Fluor™ 488 (antibody)
RRID:AB_2556542
This polyclonal secondary targets IgG (H+L)
View all literature mentionsCOMSOL Multiphysics (software resource)
RRID:SCR_014767
General-purpose software platform for modeling and simulating physics-based problems which accounts for coupled or multiphysics phenomena. The platform includes a set of core physics interfaces for common physics application areas such as structural analysis, laminar flow, pressure acoustics, transport of diluted species, electrostatics, electric currents, heat transfer, and Joule heating.
View all literature mentionsFiji (software resource)
RRID:SCR_002285
Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsGraphPad Prism (software resource)
RRID:SCR_002798
Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsRabbit Anti-Opsin, Blue , Unconjugated (antibody)
RRID:AB_177457
This unknown targets Opsin, Blue
View all literature mentions
