title: Inhibition of histone deacetylases 1 and 3 protects injured retinal ganglion cells.
abstract: OBJECTIVE
  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.affiliation: Hamilton Glaucoma Center and Department of Ophthalmology, University of California-San Diego, La Jolla, California 92037, USA.
authors.forename: Panida
authors.initials: P
authors.lastname: Chindasub
authors.forename: James D
authors.initials: JD
authors.lastname: Lindsey
authors.forename: Karen
authors.initials: K
authors.lastname: Duong-Polk
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Leung
authors.forename: Robert N
authors.initials: RN
authors.lastname: Weinreb
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D020221:Optic Nerve Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018800:Thy-1 Antigens / Q000235:genetics; D000099186:Histone Deacetylase 3
chemical_list: D001549:Benzamides; D049452:Green Fluorescent Proteins; D056284:Histone Deacetylase 1; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D011725:Pyridines; D018800:Thy-1 Antigens; D000099186:Histone Deacetylase 3; C485182:Cyan Fluorescent Protein; C118739:entinostat; C484389:Hdac1 protein, mouse