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Change in prostaglandin expression levels and synthesizing activities in dry eye disease

Authors
 Jongwoo Shim  ;  Changhun Park  ;  Hyun Soo Lee  ;  Min Soo Park  ;  Hyung Taek Lim  ;  Sunil Chauhan  ;  Reza Dana  ;  Hyon Lee  ;  Hyung Keun Lee 
Citation
 OPHTHALMOLOGY, Vol.119(11) : 2211-2219, 2012 
Journal Title
 OPHTHALMOLOGY 
ISSN
 0161-6420 
Issue Date
2012
MeSH
Adult ; Aged ; Aged, 80 and over ; Animals ; Case-Control Studies ; Chromatography, High Pressure Liquid ; Cornea/metabolism ; Cross-Sectional Studies ; Cyclooxygenase 1/genetics ; Cyclooxygenase 2/genetics ; Dinoprostone/genetics ; Dinoprostone/metabolism* ; Disease Models, Animal ; Dry Eye Syndromes/metabolism* ; Epoprostenol/genetics ; Epoprostenol/metabolism* ; Female ; Humans ; Immunoenzyme Techniques ; Intramolecular Oxidoreductases/genetics ; Lacrimal Apparatus/metabolism ; Lipocalins/genetics ; Male ; Meibomian Glands/metabolism ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Prostaglandin D2/genetics ; Prostaglandin D2/metabolism* ; Prostaglandin-E Synthases ; RNA, Messenger/metabolism ; Real-Time Polymerase Chain Reaction ; Severity of Illness Index ; Tandem Mass Spectrometry ; Tears/metabolism*
Keywords
Adult ; Aged ; Aged, 80 and over ; Animals ; Case-Control Studies ; Chromatography, High Pressure Liquid ; Cornea/metabolism ; Cross-Sectional Studies ; Cyclooxygenase 1/genetics ; Cyclooxygenase 2/genetics ; Dinoprostone/genetics ; Dinoprostone/metabolism* ; Disease Models, Animal ; Dry Eye Syndromes/metabolism* ; Epoprostenol/genetics ; Epoprostenol/metabolism* ; Female ; Humans ; Immunoenzyme Techniques ; Intramolecular Oxidoreductases/genetics ; Lacrimal Apparatus/metabolism ; Lipocalins/genetics ; Male ; Meibomian Glands/metabolism ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Prostaglandin D2/genetics ; Prostaglandin D2/metabolism* ; Prostaglandin-E Synthases ; RNA, Messenger/metabolism ; Real-Time Polymerase Chain Reaction ; Severity of Illness Index ; Tandem Mass Spectrometry ; Tears/metabolism*
Abstract
OBJECTIVE: To investigate the expression level of prostaglandins (PGs) and their de novo synthesis in dry eye (DE) disease. DESIGN: Cross-sectional case-control study and in vivo mouse experimental study. PARTICIPANTS: 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). MAIN OUTCOME MEASURES: 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.
Files in This Item:
T201205088.pdf Download
DOI
22858125
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
Yonsei Authors
Park, Min Soo(박민수) ORCID logo https://orcid.org/0000-0002-4395-9938
Lee, Hyung Keun(이형근) ORCID logo https://orcid.org/0000-0002-1123-2136
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91596
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