title: Immunopathologic processes in sympathetic ophthalmia as signified by microRNA profiling.
abstract: OBJECTIVE
  Recent discovery of microRNAs and their negative gene regulation have provided new understanding in the pathogenesis of inflammatory diseases. This study demonstrated microRNA expression profiling and their likely role in sympathetic ophthalmia, using formalin-fixed, paraffin embedded samples.
  
  
  METHODS
  Two groups of four enucleated globes (total eight globes) from patients with clinical and histopathological diagnosis of SO (experimental samples) and one group of four age-matched, noninflamed enucleated globes (control samples) were used. Human genome-wide microRNA PCR array was performed and results were subjected to bioinformatics calculation and P values stringency tests. The targets were searched using the recently published and periodically updated miRWalk software. Quantitative real-time PCR and immunohistochemical staining were performed to confirm the validated targets in the mRNA and in the protein levels, respectively.
  
  
  RESULTS
  No microRNA was significantly upregulated in SO, but 27 microRNAs were significantly downregulated. Among these, four microRNAs (hsa-miR-1, hsa-let-7e, hsa-miR-9, and hsa-miR-182) were known to be associated with the inflammatory signaling pathway. Only hsa-miR-9 has the validated targets, tumor necrosis factor-α, and nuclear factor kappa B1, which have been previously shown to be associated with mitochondrial oxidative stress-mediated photoreceptor apoptosis in eyes with SO.
  
  
  CONCLUSIONS
  Identification of altered levels of microRNAs by microRNA expression profiling may yield new insights into the pathogenesis of SO by disclosing specific microRNA signatures. In the future these may be targeted by synthetic microRNA mimic-based therapeutic strategies.
authors.affiliation: Doheny Eye Institute, Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Guey Shuang
authors.initials: GS
authors.lastname: Wu
authors.forename: Sindhu
authors.initials: S
authors.lastname: Saraswathy
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Vasconcelos-Santos
authors.forename: Narsing A
authors.initials: NA
authors.lastname: Rao
mesh_terms: D000328:Adult; D000368:Aged; D002829:Choroid / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009879:Ophthalmia, Sympathetic / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II