Recapitulating the architectural and cellular organization of the retina has been challenging, but biology hints at the possibility with the formation of eye cups and organoids. However, these structures are not amenable to high throughput screening approaches which are critical to developing new understanding and therapies, nor do they develop normal structures such as the optic nerve.
Approaches for making complex tissue models include photolithography, 3D printing, and bioprinting. These allow one to develop patterns and architectures that are seen in vivo, but they require materials and processes are not always compatible with retinal cells and progenitors due shearing forces associated with many of the 3D printing technologies and UV light for the photopolymerizable approaches.
We have developed an alternative approach based on screen printing tissue models that avoids UV light and the shearing issue. It is simple, reproducible, and highly scalable, making it suitable for high throughput assays. We have shown that we can print both a range of gels and cells in complex patterns with high resolution and reproducibility. This allows us to recapitulate the layers of the retina and to provide the matrix cues to promote the critical polarization of the cells types and promote the formation of appropriate synapses in the system, and enhanced survival of target neurons.
By coupling this approach with human RPE cells and human adult neural stem cells derived from the eye and optic nerve which have been shown to express markers for the major retinal cell types, we can make a system that models the 3D retina and optic nerve structures in a scalable and reproducible manner that is exceptionally well suited to high throughput screening approaches for understanding and treating diseases of the retina.