Document Detail

alpha-Aminoadipate induces progenitor cell properties of Müller glia in adult mice.
MedLine Citation:
PMID:  18326742     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Retinal Müller glia in higher vertebrates have been reported to possess progenitor cell properties and the ability to generate new neurons after injury. This study was conducted to determine the signals that can activate this dormant capacity of Müller glia in adult mice, by studying their behavior during glutamate stimulation.
METHODS: Various concentrations of glutamate and its analogue alpha-aminoadipate, which specifically binds Müller glia, were injected subretinally in adult mice. Proliferating retinal cells were labeled by subretinal injection of 5'-bromo-2'-deoxyuridine (BrdU) followed by immunohistochemistry. Müller cell fates were analyzed in retinal sections by using double immunolabeling with primary antibodies against Müller and other retina-specific cell markers. The effects of glutamate and alpha-aminoadipate were also determined in purified Müller cell cultures.
RESULTS: Although high levels of glutamate induce retinal damage, subtoxic levels of glutamate directly stimulate Müller glia to re-enter the cell cycle and induce neurogenesis in vivo and in purified Müller cell cultures. alpha-Aminoadipate, which selectively target glial cells, also induced expression of progenitor cell markers by Müller cells in vitro or stimulated Müller cell migration to the outer nuclear layer (ONL) and to differentiate into photoreceptors in vivo.
CONCLUSIONS: Mature Müller glia in adult mice can be induced to dedifferentiate, migrate, and generate new retinal neurons and photoreceptor cells by alpha-aminoadipate or glutamate signaling. The results of this study suggest a novel potential strategy for treating retinal neurodegeneration, including retinitis pigmentosa and age-related macular degeneration, without transplanting exogenous cells.
Masumi Takeda; Akira Takamiya; Jian-Wei Jiao; Kin-Sang Cho; Simon G Trevino; Takahiko Matsuda; Dong F Chen
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  49     ISSN:  0146-0404     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-03-10     Completed Date:  2008-04-15     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1142-50     Citation Subset:  IM    
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MeSH Terms
2-Aminoadipic Acid / pharmacology*
Bromodeoxyuridine / metabolism
Carrier Proteins / metabolism
Cell Cycle / drug effects
Cell Differentiation / drug effects*
Cell Proliferation / drug effects
Cells, Cultured
Excitatory Amino Acid Antagonists / pharmacology*
Fluorescent Antibody Technique, Indirect
Glutamic Acid / pharmacology
Mice, Inbred C57BL
Neuroglia / cytology*,  metabolism
Recoverin / metabolism
Retina / cytology*
Stem Cells / cytology*,  metabolism
Grant Support
P30 EY003790/EY/NEI NIH HHS; R01 EY017641/EY/NEI NIH HHS; R01 EY017641/EY/NEI NIH HHS; R01 EY017641-01A2/EY/NEI NIH HHS
Reg. No./Substance:
0/11-cis-retinal-binding protein; 0/Carrier Proteins; 0/Excitatory Amino Acid Antagonists; 135844-11-0/Recoverin; 1K7B1OED4N/2-Aminoadipic Acid; 3KX376GY7L/Glutamic Acid; G34N38R2N1/Bromodeoxyuridine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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