Müller glia are a potential source of neural regeneration in the postnatal chicken retina

Abstract

The retina of warm-blooded vertebrates is believed to be incapable of neural regeneration. Here we provide evidence that the retina of postnatal chickens has the potential to generate new neurons. In response to acute damage, numerous Müller glia re-entered the cell cycle, and shortly thereafter, expressed CASH-1, Pax6 and Chx10, transcription factors expressed by embryonic retinal progenitors. These progenitor-like cells transiently expressed neurofilament. Newly formed cells became distributed throughout the inner and outer nuclear layers of the retina, and remained for at least three weeks after damage. Some of these newly formed cells differentiated into retinal neurons, a few formed Müller glia, and most remained undifferentiated, with continued expression of Pax6 and Chx10. These cells continued to proliferate when grown in culture, with some differentiating into retinal neurons or Müller glia. We propose that, in response to damage, Müller glia in the retina are a potential source of neural regeneration.

Zebrafish: A model system for the study of eye genetics

“…Recent experimental evidence suggests that a subset of the Muller glia constitute an INL population of progenitor cells in fish and other vertebrates (Bernardos, et al, 2007;Fausett and Goldman, 2006;Fimble, et al, 2007;Reh, 2001 &Ooto, et al, 2004;Yurco and Cameron, 2005). In teleosts including zebrafish, mechanical damage, chemical toxicity, and phototoxicity stimulated an increase in proliferation of cells in the INL and ONL (Fausett and Goldman, 2006;Vihtelic and Hyde, 2000;Vihtelic, et al, 2006;Wu et al, 2001).…”

NeuroD induces the expression of visinin and calretinin by proliferating cells derived from toxin‐damaged chicken retina

“…We have shown previously that Nmethyl-D-aspartate (NMDA)-induced excitotoxicity causes Mü ller glia to re-enter the cell cycle, acquire phenotypes common to retinal progenitors, and generate some new neurons (Fischer and Reh, 2001a). Most cells produced by proliferating Mü ller glia-derived progenitor cells have persistent expression of Pax6 and Chx10 up to 3 weeks after toxin treatment in vivo and do not express proteins of differentiated retinal neurons or glia (Fischer and Reh, 2001a).…”

“…Most cells produced by proliferating Mü ller glia-derived progenitor cells have persistent expression of Pax6 and Chx10 up to 3 weeks after toxin treatment in vivo and do not express proteins of differentiated retinal neurons or glia (Fischer and Reh, 2001a).…”

“…In addition, we have shown that acute damage or intraocular injections of insulin and FGF2 stimulate Mü ller glia in the chick retina to proliferate, become progenitor-like cells, and produce new neurons and glia (Fischer and Reh, 2001a;Fischer et al, 2002). In the chick retina, however, regardless of whether glial proliferation is stimulated by damage or injections of growth factors, the majority of Mü ller glia-derived cells remain as undifferentiated progenitor-like cells (Fischer and Reh, 2001a;Fischer et al, 2002). It is possible that the undifferentiated cells lack a key component of the neurogenic program.…”

Manipulation of Neural Precursors in situ Induction of Neurogenesis in the Neocortex of Adult Mice

“…Lesioned postnatal avian retina undergoes some neurogenesis, with the new neurons most likely arising from Muller glia (Fischer and Rey 2001). In songbirds, new neurons are constantly added to the high vocal center (Nottebohm 1985;Alvarez-Buylla et al 1990), a portion of the brain necessary for the production of learned song (Nottebohm et al 1976;Simpson and Vicario 1990;Williams et al 1992), as well as to specific regions elsewhere in the brain, (but not all neuronal populations).…”