Change in Prostaglandin Expression Levels and Synthesizing Activities in Dry Eye Disease

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Change in Prostaglandin Expression Levels and Synthesizing Activities in Dry Eye Disease

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Title: Change in Prostaglandin Expression Levels and Synthesizing Activities in Dry Eye Disease
Author: Shim, Jongwoo; Park, Changhun; Lee, Hyun Soo; Park, Min Soo; Lim, Hyung Taek; Chauhan, Sunil Kumar; Dana, Reza; Lee, Hyon; Lee, Hyung Keun

Note: Order does not necessarily reflect citation order of authors.

Citation: Shim, Jongwoo, Changhun Park, Hyun Soo Lee, Min Soo Park, Hyung Taek Lim, Sunil Chauhan, Reza Dana, Hyon Lee, and Hyung Keun Lee. 2012. “Change in Prostaglandin Expression Levels and Synthesizing Activities in Dry Eye Disease.” Ophthalmology 119 (11) (November): 2211–2219. doi:10.1016/j.ophtha.2012.05.038.
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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). Nanoliquid 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.

Financial Disclosure(s)

The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Published Version: 10.1016/j.ophtha.2012.05.038
Other Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689228/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34428276
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