Abstract
Meibomian gland (MG) dysfunction is the leading cause of evaporative dry eye and it leads to inflammation of the ocular surface. Eicosanoids may be involved in inflammation of dry eye. This study aimed to profile tear eicosanoid levels in healthy individuals and those with MG dysfunction, and to examine if these levels are associated with clinical factors and expressibility of MG. Forty participants with MG dysfunction and 30 healthy controls were recruited in this study. Clinical signs of MG dysfunction were assessed, and tear lactoferrin concentration was evaluated. Tear eicosanoids were extracted from Schirmer’s strips and analyzed using mass spectrometry. We were able to quantify 38 tear eicosanoids and levels were increased in older individuals. In participants with MG dysfunction, higher 5-HETE, LTB4, 18-HEPE, 12-HEPE and 14-HDoHE were associated with poorer MG expressibility. The eicosanoids PGF2α, 18-HEPE, 20-HDoHE and 17-HDoHE were elevated with increased corneal staining; higher 5-HETE, LTB4 were associated with lower tear lactoferrin levels. The receiver-operating-characteristics analysis shows higher levels of 5-HETE, LTB4 and 18-HEPE were able to predict poor expressibility of MGs. In conclusion, tear eicosanoid levels are age-dependent and specific eicosanoids may be indicators of clinical obstruction of MG or the severity of ocular surface damage.
Highlights
According to the Tear Film and Ocular Surface Society Dry Eye WorkShop 2 definition, “Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological role”[1]
Eicosapentaenoic (EPA) (20:5n-3) and Docosahexaenoic (DHA) (22:6n-3) acids are widely involved in the production of anti-inflammatory eicosanoids, such as hydroxy-eicosapentaenoic acids (HEPEs) and hydroxydocosahexaenoic acids (HDoHEs) respectively[12]
We found that elevation of three of these eicosanoids: 5-hydroxy-eicosatetraenoic acids (HETEs), LTB4 and 18-HEPE or a combination of these were able to predict reduced meibomian gland expressibility (Fig. 4)
Summary
According to the Tear Film and Ocular Surface Society Dry Eye WorkShop 2 definition, “Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological role”[1]. Eicosanoids are locally acting bioactive signaling lipids derived from polyunsaturated fatty acids (PUFAs)[7] Such metabolites are formed through the action of cyclooxygenases (COX), lipoxygenases (LOX), cytochrome P450 monooxygenases (CYP450) or free radical oxidation mechanisms[8]. The greater the severity of meibomian gland obstruction, the more likely that lipids retained in the glands accumulate, and undergo enzymatic changes to increase levels of eicosanoids in the meibum[13]. This may emerge as higher concentration of eicosanoid. Since inflammation plays an etiological role in dry eye[16], the pro-inflammatory changes on the ocular surface epithelia may include upregulation of enzymes such as COX and LOX and increased levels of downstream eicosanoids. The precursors of eicosanoids, the essential omega-3 and omega-6 fatty acids, have been used in the treatment of dry eye[21]
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