Retinal stem cells in vertebrates: parallels and divergences

Abstract

During the development of the nervous system, after a given number of divisions, progenitors exit the cell cycle and differentiate as neurons or glial cells. Some cells however do not obey this general rule and persist in a progenitor state. These cells, called stem cells, have the ability to self-renew and to generate different lineages. Understanding the mechanisms that allow stem cells to "resist" differentiating stimuli is currently one of the most fascinating research areas for biologists. The amphibian and fish retinas, known to contain stem cell populations, have been pioneering models for neural stem cell research. The Xenopus retina enabled the characterization of the genetic processes that occur in the path from a pluripotent stem cell to a committed progenitor to a differentiated neuron. More recently, the discovery that avian and mammalian retinas also contain stem cell populations, has contributed to the definitive view of the adult nervous system of upper vertebrates as a more dynamic and plastic structure than previously thought. This has attracted the attention of clinicians who are attempting to employ stem cells for transplantation into damaged tissue. Research in this area is promising and will represent a key instrument in the fight against blindness and retinal dystrophies. In this review, we will focus primarily on describing the main characteristics of various retinal stem cell populations, highlighting their divergences during evolution, and their potential for retinal cell transplantation. We will also give an overview of the signaling cascades that could modulate their potential and plasticity.

Continued growth and circuit building in the anamniote visual system

“…This is similar to the way a tree grows by adding annular rings of cells around the circumference of its trunk. Cells of the CMZ are organized with the youngest and least determined stem cells nearest the periphery, the proliferative neuroblasts in the middle, and the differentiating neurons juxtaposed to mature neurons of the central retina [reviewed in (Amato et al, 2004); Fig. 1].…”

“…Comparisons of organisms along the vertebrate family tree from fish to mammals show that the anatomical area that contains the CMZ, tends to shrink as organisms lose life-long neurogenic capacity. For example, when tadpoles metamorphose into adult frogs, the number of cells within the CMZ decreases (Amato et al, 2004) and the posthatch chicken retina contains a CMZ with limited neurogenic potential that progressively loses its ability to generate new neurons and glia [e.g., (Fischer and Reh, 2000)]. Like the retinae of all mammals, those of the postnatal mouse do not grow after birth and do not appear to contain a CMZ (Amato et al, 2004).…”

The zebrafish flotte lotte mutant reveals that the local retinal environment promotes the differentiation of proliferating precursors emerging from their stem cell niche

“…In these animals, after the onset of neurogenesis in the central retina, neurons are added to the eye from a population of proliferating progenitors located at the retinal periphery in a stem cell niche termed the ciliary marginal zone (CMZ). The developmental history of embryonic retinal neurons is spatially recapitulated in the CMZ, such that the youngest and least determined cells are found nearest the periphery, the proliferative retinoblasts in the middle, and the differentiating cells closest to the central retina (reviewed by Amato et al, 2004;Perron et al, 1998).…”

Stem Cells and the Retina – Challenges for Regenerative Medicine

“…Ten years ago, evidence of a potential population of retinal stem cells is obtained in Mammals, even if it is not possible to identify a proliferating CMZ as in fishes and amphibians (Amato et al, 2004). In Mammals, two different types of cells are present in the adult eye that represent potential retinal stem cells: cells of the ciliary body (ciliary margin) and of the iris epithelium.…”