Modeling the human retina in a dish: Advances and future directions

Human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, can be directed to self-organize into three-dimensional retinal organoids that recapitulate the development, cellular architecture, and key functional features of the human retina. These organoids provide a powerful in vitro platform that models key stages of human retinogenesis and offers unique opportunities to study mechanisms of retinal development and disease in a human context that is not easily accessible in vivo. Recent advances in genome editing, single-cell and multiomics technologies, and bioengineering strategies have further expanded the potential of retinal organoids by enabling precise genetic manipulation, high-resolution profiling, and improved culture systems that more closely approximate native tissue environments. In this chapter, we first highlight how foundational insights from animal models of retinal development have guided the differentiation of human pluripotent stem cells into retinal organoids. We then discuss how these organoids have been applied to advance our understanding of human retinal biology and to model the pathogenesis of inherited and acquired retinal disorders. Finally, we examine emerging technologies, including organ-on-a-chip systems, biomaterial scaffolds, and 3D printing, that promise to refine the fidelity and translational potential of retinal organoids, setting the stage for their future role in regenerative medicine and therapeutic discovery.