title: Evaluation of lipid oxidative stress status and inflammation in atopic ocular surface disease.
abstract: BACKGROUND
  Although the oxidative stress status in atopic skin disease has been reported to be elevated, there are still no studies related to the status of oxidative stress in atopic ocular surface disease. The purpose of this study was to evaluate the ocular surface lipid oxidative stress status and inflammation in atopic keratoconjunctivitis (AKC) patients and normal subjects.
  
  
  METHODS
  Twenty eight eyes of 14 patients (9 males, 5 females) with AKC and 18 eyes of 9 age and sex matched (4 males and 5 females) normal healthy controls were examined in this prospective study. The severity of atopic dermatitis (AD) was scored by the SCORing Atopic Dermatitis (SCORAD) index. All subjects underwent Schirmer test, tear film break up time (BUT), fluorescein/Rose Bengal stainings, tear collection, and brush cytology from the upper palpebral conjunctiva. The brush cytology samples were stained with Diff-Quik for differentiation of inflammatory cells and immunohistochemistry (IHC) staining with HEL (hexanoyl-lysine) and 4-HNE (4-hydroxy-2-nonenal) to study lipid oxidation. HEL and cytokine (interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ)) levels were measured by enzyme-linked immunosorbent assay (ELISA) from tear samples of AKC patients and control subjects. Toluidine Blue and IHC staining with HEL, 4-HNE and cluster of differentiation 45 (CD45) were performed on papillary samples of AKC patients. This study was conducted in compliance with the "Declaration of Helsinki."
  
  
  RESULTS
  The tear stability and vital staining scores were significantly worse in eyes of AKC patients (p<0.05) compared to the controls. Inflammatory cells and positively stained conjunctival epithelial cells for HEL and 4-HNE showed a significant elevation in brush cytology samples of AKC patients. Significantly higher levels of HEL and cytokines were detected in tears of AKC patients compared to controls. Papillary specimens also revealed many CD45 inflammatory cells as well as many cells positively stained with HEL and 4-HNE in IHC. A strong significant linear positive correlation between conjunctival inflammation and epithelial lipid oxidative stress status was observed. Conjunctival lipid oxidative stress also correlated strongly with tear HEL levels and epithelial damage scores.
  
  
  CONCLUSIONS
  The ocular surface disease in AKC was characterized by marked tear instability, ocular surface epithelial damage, increase in inflammatory infiltrates and presence of increased lipid oxidation.
authors.affiliation: Johnson & Johnson Ocular Surface and Visual Optics Department, Keio University School of Medicine, and Department of Ophthalmology, Kitasato Institute Hospital, Tokyo, Japan.
authors.forename: Tais H
authors.initials: TH
authors.lastname: Wakamatsu
authors.forename: Murat
authors.initials: M
authors.lastname: Dogru
authors.forename: Igarashi
authors.initials: I
authors.lastname: Ayako
authors.forename: Yoji
authors.initials: Y
authors.lastname: Takano
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Osama M A
authors.initials: OM
authors.lastname: Ibrahim
authors.forename: Naoko
authors.initials: N
authors.lastname: Okada
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Satake
authors.forename: Kazumi
authors.initials: K
authors.lastname: Fukagawa
authors.forename: Jun
authors.initials: J
authors.lastname: Shimazaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujishima
mesh_terms: D000293:Adolescent; D000328:Adult; D000447:Aldehydes / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002452:Cell Count; D002648:Child; D003228:Conjunctiva / Q000378:metabolism / Q000473:pathology; D003233:Conjunctivitis, Allergic / Q000150:complications* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000166:cytology; D019573:Epithelium, Corneal / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D050356:Lipid Metabolism; D008239:Lysine / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D013194:Staining and Labeling; D013666:Tears / Q000378:metabolism; D055815:Young Adult
chemical_list: D000447:Aldehydes; D015415:Biomarkers; D016207:Cytokines; C027576:4-hydroxy-2-nonenal; D008239:Lysine