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. 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.

Dry eye modifies the thermal and menthol responses in rat corneal primary afferent cool cells

“…Induction of dry eye in rodents, produced by either environmentally controlled arid conditions or the injection of choleratoxin B into the lacrimal gland, increased the corneal expression of inflammatory cytokines (Dursun et al 2002;Lee et al 2012;Okanobo et al 2012;Shim et al 2012;Stevenson et al 2012;Zhu et al 2009Zhu et al , 2012. However, just as nerve injury reduced cold-and menthol-evoked activity, inflammation also appears to inhibit TRPM8-mediated responses.…”

Neuropathic ocular pain: an important yet underevaluated feature of dry eye

“…28 In fact, elevated levels of PGE 2 have been found in the tears of dry eye patients as compared with controls. 50 Similarly, mice subjected to adverse environmental conditions also displayed higher cyclooxygenase 2 (COX2) and PGE synthase mRNA levels on the ocular surface. 50 In line with immune cell recruitment, T cells have been found in the conjunctivae 51 and elevated levels of inflammatory cytokines have been found in the tears of dry eye patients.…”

“…50 Similarly, mice subjected to adverse environmental conditions also displayed higher cyclooxygenase 2 (COX2) and PGE synthase mRNA levels on the ocular surface. 50 In line with immune cell recruitment, T cells have been found in the conjunctivae 51 and elevated levels of inflammatory cytokines have been found in the tears of dry eye patients. 52,53 Specifically, tear levels of IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, and tumor necrosis factor-a (TNF-a) have been found to be elevated in dry eye compared with control subjects.…”

Neuropathic symptoms of the ocular surface: dryness, pain, and itch

“…In the skin, recruitment of T cells lead to the release of specific cytokines involved in itch, namely IL-2 and IL-31 [49-51]. Many inflammatory mediators, such as TNFα, IL1, IL6 [52, 53], PGE 2 [54], MMP-9 [55], have been found elevated in the tears of DE patients. T cells have also been detected more frequently in the conjunctivae of DE patients compared to controls[56].…”