title: sPLA2-IIa amplifies ocular surface inflammation in the experimental dry eye (DE) BALB/c mouse model.
abstract: OBJECTIVE
  sPLA2-IIa is a biomarker for many inflammatory diseases in humans and is found at high levels in human tears. However, its role in ocular surface inflammation remains unclear. An experimentally induced BALB/c mouse dry eye (DE) model was used to elucidate the role of sPLA2-IIa in ocular surface inflammation.
  
  
  METHODS
  BALB/c mice were subcutaneously injected with scopolamine and placed in a daytime air-drying device for 5 to 10 days. Control mice received no treatment. DE status was evaluated with tear production with a phenol-red thread method. Tear inflammatory cytokines were quantified by multiplex immunoassays. Ocular surface inflammation and sPLA2-IIa expression were examined by immune-staining and quantitative (q)RT(2)-PCR. Conjunctiva (CNJ) of the mice was cultured for prostaglandin E2 production induced by sPLA2-IIa with various amount of sPLA2-IIa inhibitor, S-3319.
  
  
  RESULTS
  Treated mice produced fewer tears and heavier corneal (CN) fluorescein staining than the untreated controls (P < 0.001). They also revealed lower goblet cell density (P < 0.001) with greater inflammatory cell infiltration within the conjunctiva, and higher concentration of tear inflammatory cytokines than the controls. Moreover, treated mice showed heavier sPLA2-IIa immune staining than the controls in the CNJ epithelium, but not in the CN epithelium or the lacrimal gland. Treated mice exhibited upregulated sPLA2-IIa and cytokine gene transcription. Furthermore, CNJ cultures treated with sPLA2-IIa inhibitor showed significantly reduced sPLA2-IIa-induced inflammation.
  
  
  CONCLUSIONS
  This is the first report regarding sPLA2-IIa in the regulation of ocular surface inflammation. The findings may therefore lead to new therapeutic strategies for ocular surface inflammation, such as DE disease.
authors.affiliation: Department of Ophthalmology, Mount Sinai School of Medicine, New York, New York 10029, USA. yi.wei@mssm.edu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wei
authors.forename: Seth P
authors.initials: SP
authors.lastname: Epstein
authors.forename: Shima
authors.initials: S
authors.lastname: Fukuoka
authors.forename: Neil P
authors.initials: NP
authors.lastname: Birmingham
authors.forename: Xiu-Min
authors.initials: XM
authors.lastname: Li
authors.forename: Penny A
authors.initials: PA
authors.lastname: Asbell
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003228:Conjunctiva / Q000378:metabolism* / Q000473:pathology; D003315:Cornea / Q000378:metabolism* / Q000473:pathology; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D015352:Dry Eye Syndromes / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D054497:Phospholipases A2, Secretory / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013666:Tears / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D004247:DNA; D054497:Phospholipases A2, Secretory