Chapter 24 - Regenerative Medicine for Diseases of the Retina

Abstract

This chapter reviews the basic developmental biology of the eye, describing the relationships between retinal stem cells and progenitors during development, the sources of retinal stem cells, and progenitors in mature animals that mediate retinal regeneration, and explains the derivation of retinal progenitor cells from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). The vertebrate retina arises from the ventral diencephalon of the neural tube. Paired evaginations, known as the optic vesicles, emerge from the anterior region of the neural plate. The optic vesicle cells express a unique complement of transcription factors, termed eye field transcription factors (EFTFs), which set them apart from the surrounding regions of the neural plate. Retinal development involves a massive proliferation of a group of cells that occupy the structure known as the optic cup. The optic cup forms from an involution of the optic vesicle, and mutations in the EFTFs prevent the eye from progressing to this stage, or much beyond it. The multipotent progenitors make up the majority of mitotically active cells in the embryonic retina. At early stages of retinal development, these cells are competent to generate the entire complement of retinal neurons and glia, and at later stages of development their progeny become restricted to rod photoreceptors, bipolar cells, and Müller glia, the primary glial cells intrinsic to the retina and the only glia generated by the multipotent retinal progenitors.