Rapamycin Rescues Endoplasmic Reticulum Stress-Induced Dry Eye Syndrome in Mice

PURPOSE. To investigate whether rapamycin protects tear production and the ocular surface during endoplasmic reticulum (ER) stress-induced dry eye syndrome in mice. METHODS. Tunicamycin was injected intraperitoneally in BALB/c mice without or with rapamycin (TM or RM5 group). Peritoneal injection of PBS performed in vehicle group. Group without injection served as control. Blinking rate, fluorescein staining score (FSS), and phenol red thread tear production test were measured at 4 days, 1 week, and 2 weeks after treatment. Levels of inflammatory and angiogenic cytokines were measured by ELISA. RESULTS. Blinking rate and FSS were elevated, and tear production was decreased in TM group compared with controls (P < 0.05 for all), which was ameliorated by rapamycin at 1 and 2 weeks. Levels of inflammatory and angiogenic cytokines in the cornea and lacrimal glands were higher in the TM group than controls, and lower in the RM5 group than the TM group at 1 and 2 weeks (P < 0.05 for all). CONCLUSION. Rapamycin protected tear production and the ocular surface against this dry eye syndrome by ameliorating ER stress-induced vascular damage and inflammation of lacrimal glands and the ocular surface.