Stimulation of neural regeneration in the mouse retina.
Müller glia can serve as a source of new neurons after retinal damage in both fish and birds. Investigations of regeneration in the mammalian retina in vitro have provided some evidence that Müller glia can proliferate after retinal damage and generate new rods; however, the evidence that this occurs in vivo is not conclusive. We have investigated whether Müller glia have the potential to generate neurons in the mouse retina in vivo by eliminating ganglion and amacrine cells with intraocular NMDA injections and stimulating Müller glial to re-enter the mitotic cycle by treatment with specific growth factors. The proliferating Müller glia dedifferentiate and a subset of these cells differentiated into amacrine cells, as defined by the expression of amacrine cell-specific markers Calretinin, NeuN, Prox1, and GAD67-GFP. These results show for the first time that the mammalian retina has the potential to regenerate inner retinal neurons in vivo.
Karl
Mike O
MO
Department of Biological Structure, Health Science Center, University of Washington, School of Medicine, Seattle, WA 98195, USA.
Hayes
Susan
S
Nelson
Branden R
BR
Tan
Kristine
K
Buckingham
Brian
B
Reh
Thomas A
TA
D025042:Amacrine Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D064032:Calbindin 2; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D004268:DNA-Binding Proteins; D003714:Denervation; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005968:Glutamate Decarboxylase / Q000378:metabolism; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016202:N-Methylaspartate / Q000633:toxicity; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000502:physiology*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein
D015415:Biomarkers; C576511:Calb2 protein, mouse; D064032:Calbindin 2; D004268:DNA-Binding Proteins; D018690:Excitatory Amino Acid Agonists; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D064030:S100 Calcium Binding Protein G; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D049452:Green Fluorescent Proteins; D016202:N-Methylaspartate; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1