title: In vivo gene expression profiling of retina postintravitreal injections of dexamethasone and triamcinolone at clinically relevant time points for patient care.
abstract: OBJECTIVE
  To identify retinal genes and their relevant expression pathways affected by intravitreal injections of dexamethasone (Dex) and triamcinolone acetonide (TAA) in mice at clinically relevant time points for patient care.
  
  
  METHODS
  Differential gene expressions of over 34,000 well-characterized mouse genes, in the retinas of 6-week-old C57BL/6J mice, were analyzed after intravitreal steroid injections at 1 week and 1 month time points, using mouse genome microarrays. The data were analyzed using commercial microarray analysis software for biologically relevant changes in gene expression pathways.
  
  
  RESULTS
  A common gene pathway, with differentially activated genes for both steroids and time points, was "Semaphorin Signaling in Neurons," a member of the "Axonal Guidance Signaling System." At 1 week postinjection a common theme was activation of genes expressed in retinal glial cells, tumor necrosis factor-α, and transforming growth factor-β signaling pathways and upregulation of stress response proteins (Serpina3n, Cebpd), as well as neuropeptide signaling somatostatin receptor (Sstr2). Unique for Dex was the upregulation of acute phase proteins (Gfap, Cp, Edn2) as well as Plexna2, a semaphorin signaling receptor, whereas EphrinB receptor ephexin 1 (Argef15) was downregulated. Folate signaling appears to be unique for TAA at 1 week (Folh1, Cubn), whereas aryl-hydrocarbon receptor signaling might be important for both steroids at 1 month postinjection.
  
  
  CONCLUSIONS
  Understanding the molecular and genetic effects of intraocular steroid treatments is of clinical relevance. This in vivo study has elucidated several genes and pathways that are potentially altering the neuroprotective/neurodegenerative balance between glial and retinal ganglion cells during intravitreal steroid treatment.
authors.affiliation: Vitreoretinal Research Laboratory, Department of Ophthalmology, University of California Davis, Davis, California, USA.
authors.forename: Zeljka
authors.initials: Z
authors.lastname: Smit-McBride
authors.forename: Sara P
authors.initials: SP
authors.lastname: Modjtahedi
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Cessna
authors.forename: David G
authors.initials: DG
authors.lastname: Telander
authors.forename: Leonard M
authors.initials: LM
authors.lastname: Hjelmeland
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Morse
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D023281:Genomics; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000235:genetics*; D018696:Neuroprotective Agents / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D014221:Triamcinolone / Q000494:pharmacology*
chemical_list: D005938:Glucocorticoids; D018696:Neuroprotective Agents; D014221:Triamcinolone; D003907:Dexamethasone