Document Detail


Inhibition of histone deacetylases 1 and 3 protects injured retinal ganglion cells.
MedLine Citation:
PMID:  23197683     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Thy-1 is a marker of retinal ganglion cell (RGC) differentiation. Optic nerve injury triggers reduction of Thy-1 promoter activation followed by retinal ganglion cell (RGC) death. This study determined whether MS-275, an inhibitor of the histone deacetylases 1 and 3, can inhibit these changes.
METHODS: Mice expressing cyan fluorescent protein (CFP) under control of the Thy-1 promoter received MS-275 (subcutaneous) or vehicle three times per week starting 1 week before optic nerve crush and continuing for 6 weeks. The same retinal area was imaged using the blue-light confocal scanning laser ophthalmoscope before and after optic nerve crush every week, and fluorescent spots were counted manually. The eyes were then processed for histopathologic analysis.
RESULTS: The mean proportions of fluorescent retinal neurons remaining in the vehicle group following optic nerve crush were 36 ± 8, 18 ± 6, 13 ± 10, 12 ± 4, 13 ± 5, and 13 ± 5% at weeks 1 through 6, respectively (n = 6). In contrast, the mean proportions of fluorescent retinal neurons remaining in the group treated with MS-275 were 59 ± 19, 39 ± 11, 34 ± 12, 33 ± 15, 32 ± 13, and 27 ± 15% at weeks 1 through 6, respectively (n = 7, P < 0.05 at weeks 1 through 5). Rate analysis showed that MS-275 slowed the rate of loss during the first 2 weeks by 23% (P < 0.05) and subsequently was similar. Histopathologic analysis revealed 27 ± 13% greater ganglion cell layer (GCL) neurons in the eyes from mice that received MS-275 treatment (P < 0.02).
CONCLUSIONS: These results indicate that treatment with MS-275 protects against the loss of RGC differentiation and promotes RGC survival following optic nerve injury.
Authors:
Panida Chindasub; James D Lindsey; Karen Duong-Polk; Christopher K Leung; Robert N Weinreb
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-07
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  54     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-08     Completed Date:  2013-03-05     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  96-102     Citation Subset:  IM    
Affiliation:
Hamilton Glaucoma Center and Department of Ophthalmology, University of California-San Diego, La Jolla, California 92037, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, Thy-1 / genetics
Benzamides / pharmacology*
Body Weight / drug effects
Cell Differentiation / drug effects
Cell Survival / drug effects
Female
Green Fluorescent Proteins / genetics
Histone Deacetylase 1 / antagonists & inhibitors*,  metabolism
Histone Deacetylase Inhibitors / pharmacology*
Histone Deacetylases / metabolism*
Male
Mice
Mice, Mutant Strains
Optic Nerve Injuries / drug therapy*,  metabolism,  pathology
Pyridines / pharmacology*
Retinal Ganglion Cells / drug effects*,  enzymology,  pathology
Grant Support
ID/Acronym/Agency:
R01 EY019692/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Thy-1; 0/Benzamides; 0/Cyan Fluorescent Protein; 0/Histone Deacetylase Inhibitors; 0/Pyridines; 0/entinostat; 147336-22-9/Green Fluorescent Proteins; EC 3.5.1.98/Hdac1 protein, mouse; EC 3.5.1.98/Histone Deacetylase 1; EC 3.5.1.98/Histone Deacetylases; EC 3.5.1.98/histone deacetylase 3
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