The rod photoreceptor lineage of teleost fish

Abstract

The retinas of postembryonic teleost fish continue to grow for the lifetime of the fish. New retinal cells are added continuously at the retinal margin, by stem cells residing at the circumferential germinal zone. Some of these retinal cells differentiate as Müller glia with cell bodies that reside within the inner nuclear layer. These glia retain some stem cell properties in that they carry out asymmetric cell divisions and continuously generate a population of transit-amplifying cells – the rod photoreceptor lineage – that are committed to rod photoreceptor neurogenesis. These rod progenitors progress through a stereotyped sequence of changes in gene expression as they continue to divide and migrate to the outer nuclear layer. Now referred to as rod precursors, they undergo terminal mitoses and then differentiate as rods, which are inserted into the existing array of rod and cone photoreceptors. The rod lineage displays developmental plasticity, as rod precursors can respond to the loss of rods through increased proliferation, resulting in rod replacement. The stem cells of the rod lineage, Müller glia, respond to acute damage of other retinal cell types by increasing their rate of proliferation. In addition, the Müller glia in an acutely damaged retina dedifferentiate and become multipotent, generating new, functional neurons. This review focuses on the cells of the rod lineage and includes discussions of experiments over the last 30 years that led to their identification and characterization, and the discovery of the stem cells residing at the apex of the lineage. The plasticity of cells of the rod lineage, their relationships to cone progenitors, and the applications of this information for developing future treatments for human retinal disorders will also be discussed.

A self-renewing division of zebrafish Müller glial cells generates neuronal progenitors that require N-cadherin to regenerate retinal neurons

“…In the teleost retina, neurogenesis continues not only in the CMZ, but also in central retina. Müller glia exhibit astrocytic properties (Bringmann et al, 2006), but in addition to physiological and structural support of the retina, they also function similar to radial glia of the embryonic mammalian cortex (Götz and Huttner, 2005;Kriegstein and Alvarez-Buylla, 2009); they divide slowly and sporadically to generate fate-restricted rod progenitors that migrate apically along the radial glial process and differentiate into rod photoreceptors (Raymond and Rivlin, 1987;Bernardos et al, 2007;Stenkamp, 2011).…”

Morphology of the Eyeball, Orbit and Retina of Atlantic Salmon (Salmo Salar) Alevins under Hypoxic Conditions

“…The peripheral retina has a proliferative germanitive zone (PGZ), similar to that described by Ottenson & Hitchcock, who said that all the retinal cell types except the rods are formed from the PGZ. In the adult retina Stenkamp (2011) says that new cells are generated from two retinoblast populations, the PGZ and the lineage of rod progenitors. Queiroz (2007) and Sánchez González (2009) say that from the PGZ concentric rings of cells are added to the retina that mature and are different, so the cells that are in the more peripheral regions of the retina will be the youngest.…”

Development of the Vertebrate Eye and Retina

“…CGZ-like characteristics have been described to exist at the retinal margin in mammals (Kubota, Hokoc, Moshiri, McGuire, & Reh, 2002), although their location in the periphery makes them inconvenient as potential sources of new neurons in treatment of any retinal disease that affects central vision. A second aspect of persistent neurogenesis in zebrafish is the continuous generation of new rod photoreceptors by a dedicated lineage of cells known as the rod lineage (Stenkamp, 2011). At the apex of this lineage – the stem cell – is the Műller glial cell (MG), which generates progenitors that proliferate within the INL (a transit-amplifying population), migrate to the ONL, then undergo terminal mitosis and differentiate as rods (Bernardos et al, 2007) (Fig.…”

“…Bottom, right: Following damage, Müller glia become multipotent, and contribute to the neurogenesis of all retinal neuronal types (Pathway B). Figure reproduced from (Stenkamp, 2011), with permission.…”