The outer retina, consisting of the light-sensing photoreceptors and the overlying retinal pigment epithelium (RPE), are affected in a number from retinal degenerative conditions. Developing strategies to maintain the function and cellular homeostasis of the outer retina requires a better understanding of the degenerative process. The creation of valid in vitro disease model for a number of retinal degenerations would require an organized 3D state such as that existing in the eye in order to mimic its highly-differentiated characteristics. Our solution to this challenge is to combine our expertise in retinal differentiation of iPSCs and combine it with our recent work on using hydrogels as bioscaffolds to promote 3D organization and lamination. This in turn should lead to maturation and generation of organized bilayered retina upon printing over a monolayer of mature RPE. We have previously published work on generating various retinal cells from human pluripotent stem cells (embryonic stem cells and induced pluripotent stem cells) in 2D monolayer culture setting. In this proposed solution, we will develop technologies to generate human retina in a dish by combining human induced pluripotent stem cell technologies with hydrogel based biomaterials. We propose to generate a Gelatin methacrylate (GelMA) based-bioink for three reasons: (i) it is biocompatible with human retinal cells, (ii) it provides support to the retinal cells through ECM adjuvants to promote lamination and (iii) it is extrudable through 3D printers. By optimizing this hydrogel-based bioink, we aim to print human retinal tissue over iPSC-derived retinal pigment epithelial layer to promote tissue interaction which is critical for maturation of photoreceptors.
Long-term implications of this solution include the ability to use the proposed technology to study both retinal development as well as human disease modeling in a dish. It also has high-throughput screening applications as it is adapted to be used with multi-well 3D bioprinters.