| Purpose: Dry Eye is a common inflammatory and autoimmune ocular surface disease, and common in women. No efficient therapy has been developed due to its complicated mechanism and risk factor. Even though the pro-resolving role has been widely appreciated in recent year, there’s no enough evidence from animal experiment to prove its benefit role in dry eye treatment. In the present study, we investigated if SPM circuits are expressed and functional in the eyelid and conjunctiva and exhibit sex-specific differences in Dry Eye. In addition, the regulatory role of Rv D1 in dry eye resolution phase was investigated too.Method: 1. The establishment in mouse model of dry eye and the evaluation of its effectiveness The experimental animals were C57BL/6 female mice at the age of six to eight weeks. 20 mice were randomly divided into 4 groups, 3 of them were used for the experiment of 3 days, 5 days and 10 days dry eye models respectively, and another was set as control group. 2. The influence on lipid mediators in eyelid tissue of dry eye and its gender differences The mouse models of dry eye used male and female C57BL/6 mice at the same age(6-8 weeks). Each 15 male and female mice were randomly divided into control group, 5 days and 10 days model groups. Use LC-MS/MS to analysis lipid samples. Myeloperoxidase(MPO) activity experiment, flow cytometry and real-time fluorescent quantitative polymerase chain reaction(Real-time PCR) were used 3. The influence and regulation of resolvin Rv D1 on ocular surface disease in experimental dry eye healing phase Twenty C57BL/6 female mice at the same age(6-8 weeks) were randomly divided into normal control group, 10 days dry eye model group, Rv D1-intervention group, and non-intervention control group. The last two groups of mice were set to thenormal environment after 10 days of modeling process, local and systematically injected Rv D1 and placebo, respectively.Results: 1. Tear secretion and goblet cells density decreased in mouse models of 5 days and 10 days groups compared with the control group, the differences were statistically significant(P<0.01). 2. The DHA, 17-HDHA and LXA4 were significantly higher in the eyelid of female mice than the male mice(P<0.0232). The conjunctival goblet cells were decreased significantly in both male and female models(P<0.0001). Meanwhile, the expression of COX-2 m RNA, which could catalytic pro-inflammatory lipid mediator synthesis, significantly increased in both male and female models comparing to control group(P<0.003). 3. The tear secretion in Rv D1-intervention group on day 1 was obviously higher than that of the control group. the difference was statistically significant(P<0.02). In addition, compared to the 10 days dry eye model group and non-intervention control group, the number of CD4+T cells in the lacrimal gland was lower in the Rv D1-intervention group.Conclusions Inflammatory lesions and the change of pro-resolving lipid mediators caused by dry eye were different between conjunctiva and eyelid, indicating the possible independent regulatory mechanism respectively. In addition, dry eye has gender specificity in the expression and adjustment of pro-resolving lipid mediators in conjunctiva and eyelid tissue. The resolvin Rv D1 has potential effect in the regulation of inflammatory immune cells, and can promote tear secretion during early healing phase of dry eye. |
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