title: Inhibition of HDAC2 protects the retina from ischemic injury.
abstract: OBJECTIVE
  Protein acetylation is an essential mechanism in regulating transcriptional and inflammatory events. Studies have shown that nonselective histone deacetylase (HDAC) inhibitors can protect the retina from ischemic injury in rats. However, the role of specific HDAC isoforms in retinal degenerative processes remains obscure. The purpose of this study was to investigate the role of HDAC2 isoform in a mouse model of ischemic retinal injury.
  
  
  METHODS
  Localization of HDAC2 in mice retinas was evaluated by immunohistochemical analyses. To investigate whether selective reduction in HDAC2 activity can protect the retina from ischemic injury, Hdac2⁺/⁻ mice were utilized. Electroretinographic (ERG) and morphometric analyses were used to assess retinal function and morphology.
  
  
  RESULTS
  Our results demonstrated that HDAC2 is primarily localized in nuclei in inner nuclear and retinal ganglion cell layers, and HDAC2 activity accounted for approximately 35% of the total activities of HDAC1, 2, 3, and 6 in the retina. In wild-type mice, ERG a- and b-waves from ischemic eyes were significantly reduced when compared to pre-ischemia baseline values. Morphometric examination of these eyes revealed significant degeneration of inner retinal layers. In Hdac2⁺/⁻ mice, ERG a- and b-waves from ischemic eyes were significantly greater than those measured in ischemic eyes from wild-type mice. Morphologic measurements demonstrated that Hdac2⁺/⁻ mice exhibit significantly less retinal degeneration than wild-type mice.
  
  
  CONCLUSIONS
  This study demonstrated that suppressing HDAC2 expression can effectively reduce ischemic retinal injury. Our results support the idea that the development of selective HDAC2 inhibitors may provide an efficacious treatment for ischemic retinal injury.
authors.affiliation: Storm Eye Institute, Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina 29425, USA. fan@musc.edu
authors.forename: Jie
authors.initials: J
authors.lastname: Fan
authors.forename: Oday
authors.initials: O
authors.lastname: Alsarraf
authors.forename: Mohammad
authors.initials: M
authors.lastname: Dahrouj
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Platt
authors.forename: C James
authors.initials: CJ
authors.lastname: Chou
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Rice
authors.forename: Craig E
authors.initials: CE
authors.lastname: Crosson
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004596:Electroretinography; D056464:Histone Deacetylase 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015427:Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D012162:Retinal Degeneration / Q000201:enzymology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C012589:trichostatin A; C533424:Hdac2 protein, mouse; D056464:Histone Deacetylase 2
keywords: HDAC2; ischemia; neuroprotection; retinal degeneration