Self-Organization of the Retina during Eye Development, Retinal Regeneration In Vivo, and in Retinal 3D Organoids In Vitro

Self-organization is a process that ensures histogenesis of the eye retina. This highly intricate phenomenon is not sufficiently studied due to its biological complexity and genetic heterogeneity. The review aims to summarize the existing central theories and ideas for a better understanding of retinal self-organization, as well as to address various practical problems of retinal biomedicine. The phenomenon of self-organization is discussed in the spatiotemporal context and illustrated by key findings during vertebrate retina development in vivo and retinal regeneration in amphibians in situ. Described also are histotypic 3D structures obtained from the disaggregated retinal progenitor cells of birds and retinal 3D organoids derived from the mouse and human pluripotent stem cells. The review highlights integral parts of retinal development in these conditions. On the cellular level, these include competence, differentiation, proliferation, apoptosis, cooperative movements, and migration. On the physical level, the focus is on the mechanical properties of cell- and cell layer-derived forces and on the molecular level on factors responsible for gene regulation, such as transcription factors, signaling molecules, and epigenetic changes. Finally, the self-organization phenomenon is discussed as a basis for the production of retinal organoids, a promising model for a wide range of basic scientific and medical applications.