title: Ocular surface and MUC5AC alterations in atopic patients with corneal shield ulcers.
abstract: OBJECTIVE
  To describe MUC5AC alterations and the ocular surface disorder in atopic patients with or without corneal ulcers.
  
  
  METHODS
  Atopic patients' eyes were divided into two groups according to the presence and absence of corneal ulceration. The subjects underwent corneal sensitivity measurements, Schirmer test, tear film break-up time (BUT), fluorescein and Rose Bengal staining of the ocular surface and conjunctival impression cytology and brush cytology. Impression cytology samples underwent PAS and immunohistochemical staining for MUC5AC. Brush cytology specimens underwent evaluation for inflammatory cell expression and quantitative real-time PCR for MUC5AC mRNA expression. The differences related to the tear function and ocular surface examination parameters between patients with and without corneal ulceration and healthy control subjects were studied. In addition, the differences of the study parameters related to ocular surface epithelial health and inflammatory status between patient eyes with atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC) were investigated.
  
  
  RESULTS
  The mean corneal sensitivity and BUT values were significantly lower in atopic patients with corneal ulcers, compared to patients without ulcers and controls (p < 0.001). Brush cytology specimens from patients with corneal ulcers revealed significantly higher expression of inflammatory cells compared to patients without ulcers and controls (p < 0.001). Impression cytology samples from eyes with corneal ulcers showed significant squamous metaplasia and reduction in goblet cell density compared to eyes without ulcers and eyes of control subjects. The mean squamous metaplasia grade was significantly higher in eyes with AKC compared to eyes with VKC (p < 0.02). The mean goblet cell density was significantly lower in eyes with AKC compared to eyes with VKC (p < 0.01). Specimens from eyes with corneal ulcers showed PAS positive mucin pickup and did not stain positive for MUC5AC. MUC5AC mRNA expression was significantly lower in eyes with corneal ulcers compared to eyes without ulcers and eyes of control subjects. MUC5AC mRNA expression was also significantly lower in eyes with AKC compared to eyes with VKC.
  
  
  CONCLUSIONS
  Ocular surface inflammation, tear film instability, and decreased conjunctival MUC5AC mRNA expression were thought to be important in the pathogenesis of noninfectious corneal shield ulcers in atopic ocular surface disease.
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, Shinanomachi, Tokyo, Japan.muratodooru@yahoo.com
authors.forename: Murat
authors.initials: M
authors.lastname: Dogru
authors.forename: Naoko
authors.initials: N
authors.lastname: Asano-Kato
authors.forename: Mari
authors.initials: M
authors.lastname: Tanaka
authors.forename: Ayako
authors.initials: A
authors.lastname: Igarashi
authors.forename: Shigeto
authors.initials: S
authors.lastname: Shimmura
authors.forename: Jun
authors.initials: J
authors.lastname: Shimazaki
authors.forename: Naoko
authors.initials: N
authors.lastname: Okada
authors.forename: Yoji
authors.initials: Y
authors.lastname: Takano
authors.forename: Kazumi
authors.initials: K
authors.lastname: Fukagawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujishima
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D003228:Conjunctiva / Q000473:pathology*; D003315:Cornea / Q000503:physiopathology; D003320:Corneal Ulcer / Q000209:etiology / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D020397:Goblet Cells / Q000473:pathology; D006801:Humans; D006967:Hypersensitivity / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D008679:Metaplasia; D055271:Mucin 5AC; D009077:Mucins / Q000235:genetics / Q000378:metabolism*; D010503:Periodic Acid-Schiff Reaction; D010812:Physical Stimulation; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012677:Sensation; D013194:Staining and Labeling; D013666:Tears / Q000378:metabolism
chemical_list: C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D012333:RNA, Messenger