Development of a 3-dimensional microphysiological Retina-on-a-chip system

Abstract

Purpose : Retinal disorders such as age-related macular degeneration or retinitis pigmentosa are a leading cause for blindness and curative treatment options are currently not available. Basic research on disease mechanisms involved in the pathology as well as the development of new pharmacological treatment options require reproducible and accessible model systems that accurately represent the physiological situation in humans. Existing retinal model systems such as retinal explants or animal models are either hardly accessible and not suitable for long-term culture or differ substantially from the human physiology. Both, therefore, do not represent an accurate model system. Retinal organoids are 3-dimensional organ-like structures that can be derived from human pluripotent stem cells and feature all major retinal cell types as well as a retinal layering that closely resembles the human in vivo situation. Nevertheless, retinal organoids are still restricted in their applicability as a model system, due to limitations in retinal connectivity and maturation as well as reproducibility issues due to variability of culture conditions or insufficient media supply.

Methods : To overcome these limitations, we have combined retinal organoids with microfluidic organ-on-a-chip technology to develop a 3D Retina-on-a-chip (3D RoC). The 3D RoC enables the co-culture of retinal organoids with retinal pigment epithelium (RPE) and other cell types to create a defined physiological microenvironment providing optimized and reproducible culture conditions.

Results : We have successfully integrated retinal organoids and RPE derived from human induced pluripotent stem cells into the chips and were able to show viability and physiological interactions, essential for nutrition, survival and normal metabolism of the retina.

Conclusions : In summary, we present an in vitro culture system with physiological structure and function, which represents a new and powerful model system for future studies on retinal development, pathology and pharmaceutical treatment.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.