Determinants of molecular mechanisms in neuroretinal development

Abstract

Increasing understanding about retinal development is not an academic curiosity alone; the developmental pathways may hold the key to the success of regenerative and reconstructive therapies being investigated to combat retinal degeneration. Development of the retina is a highly organized process. Retinal pigment epithelium (RPE), as well as the neural retina, develops from neuroectoderm. The neural retina itself comprises a number of functionally and morphologically diverse neurons and the radial glia, the Müller cells. Retinal progenitors give rise to this diverse array of cells. The ontogenic development of retinal neurons is defined and preserved across species. The sequence of neuronal birth in retina follows the phylogenetic evolution of these neurons. This is achieved by cues from environment and perhaps increasingly restricted potential of the retinal progenitors. Retinal cells are generated in two waves. In the first wave, neurons of the cone pathways that are phylogenetically older are generated, whereas the second gives rise to the neurons of rod pathways, which developed later during evolution. Proliferation in the early stages of retinal development produces progenitors that are able to migrate laterally. In the later stages, when the cells of rod pathways are generated, the postmitotic cells migrate only radially on the scaffold provided by the Müller cell. Subsequently, specific connections and synapses are formed and the plexiform layers develop. The processes of the nonprojecting neurons of the retina are guided toward the partners on the railroads provided by the Müller cell processes. This happens due to the differential expression of cell adhesion molecules perhaps on the Müller cells. Cell adhesion molecules participate not only in guiding the neurites, but also in their growth. There is also evidence that neurotransmitters might be important for various aspects of retinal organization such as cell migration, synaptogenesis, and dendritic pruning. The fully mature retina is arranged as thin sheet of cells divided into three concentric layers of cell bodies, each containing specific cell types. These layers are separated from each other by synaptic or plexiform layers containing specific retinal connections. Retinal neurons are arranged in repeating functional units spanning all retinal layers that form a mosaic across the retina. In this way, all points within the retinal field are able to sample visual signals appropriately. There is evidence that certain photoreceptors may act as a template for the development of these mosaics. In addition, migration of neurons and apoptosis also play important roles. Organization of specialized regions of the retina such as the fovea is more complex. Evidence suggests that it involves migration of neurons. How a rod-free fovea is created is a mystery. It is possible that the cytogenesis is truncated before the rods are generated. Alternatively, it is possible that some local factors induce the differentiation of the neurons generated there into the cones. Phylogenetic evolution of retinal neurons also determines the retinal circuitry. The neurons that evolved later found connections secondary to already existing ones. In this chapter, retinal development is discussed in the context of its phylogeny, ontogeny, and embryogenesis. © 2007 Springer Science+Business Media, LLC. All rights reserved.