title: Change in prostaglandin expression levels and synthesizing activities in dry eye disease.
abstract: OBJECTIVE
  To investigate the expression level of prostaglandins (PGs) and their de novo synthesis in dry eye (DE) disease.
  
  
  METHODS
  Cross-sectional case-control study and in vivo mouse experimental study.
  
  
  METHODS
  Forty-six eyes from 23 DE patients and 33 eyes from 17 age- and sex-matched controls were studied. Also, DE-induced murine eyes were compared with control eyes.
  
  
  METHODS
  Patients completed a symptom questionnaire using a 100-mm visual analog scale (VAS). Nano-liquid chromatography tandem mass spectrometry was used for the quantification of PGE2 and PGD2. A DE disease environmental chamber was used to induce DE in mice. One week after induction, enzyme expressions of cyclooxygenase-1, cyclooxygenase-2 (COX-2), PG E synthase (PGES), and PG D synthase (PGDS) in the lacrimal glands, meibomian glands, and corneas were examined using immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR).
  
  
  METHODS
  The mean PGE2 and PGD2 levels in the tears of DE patients were measured and compared with symptom severity scores. Immunohistochemistry staining patterns and qRT-PCR data of DE mice were quantified.
  
  
  RESULTS
  The mean PGE2 level in the tears of DE patients (2.72 ±3 .42 ng/ml) was significantly higher than that in the control group (0.88 ± 0.83 ng/ml; P = 0.003). However, the mean PGD2 level in the tears of DE patients (0.11 ± 0.22 ng/ml) was significantly lower (0.91 ± 3.28 ng/ml; P = 0.028). The mean PGE2-to-PGD2 ratio correlated strongly with VAS scoring (P = 0.008). In DE mice, COX-2 mRNA was significantly higher in ocular surface tissue and lacrimal glands. Furthermore, PGES mRNA was significantly higher in ocular surface tissue, whereas PGDS mRNA was decreased. Immunohistochemistry staining showed elevated COX-2 expression in the lacrimal glands, meibomian glands, corneas, and conjunctivas. Furthermore, PGES expression was found in periductal infiltrated cells of the lacrimal glands and conjunctival epithelium. Also, PGDS expression was decreased in meibomian glands and increased focally in the conjunctival epithelium.
  
  
  CONCLUSIONS
  A reciprocal change in PGE2 and PGD2 levels was found in the tears of DE patients, which correlated with patients' symptom scores. These clinical results were supported by increased COX-2 and PGES expression levels found in tear-producing tissues of DE mice.
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jongwoo
authors.initials: J
authors.lastname: Shim
authors.forename: Changhun
authors.initials: C
authors.lastname: Park
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Lee
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Park
authors.forename: Hyung Taek
authors.initials: HT
authors.lastname: Lim
authors.forename: Sunil
authors.initials: S
authors.lastname: Chauhan
authors.forename: Reza
authors.initials: R
authors.lastname: Dana
authors.forename: Hyon
authors.initials: H
authors.lastname: Lee
authors.forename: Hyung Keun
authors.initials: HK
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000378:metabolism; D003430:Cross-Sectional Studies; D051545:Cyclooxygenase 1 / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000378:metabolism*; D011464:Epoprostenol / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D007765:Lacrimal Apparatus / Q000378:metabolism; D054834:Lipocalins / Q000235:genetics; D008297:Male; D008537:Meibomian Glands / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D015230:Prostaglandin D2 / Q000235:genetics / Q000378:metabolism*; D000071876:Prostaglandin-E Synthases; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D053719:Tandem Mass Spectrometry; D013666:Tears / Q000378:metabolism*
chemical_list: D054834:Lipocalins; D012333:RNA, Messenger; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone; D015230:Prostaglandin D2