PEA Relieves Sleep Deprivation-induced Dry Eye Through Improving Lacrimal Gland Lipid Metabolism

Objective:Sleep deprivation(SD)causes abnormal lipid metabolism in the lacrimal gland of mice,causing lipid accumulation in the lacrimal gland,reducing the amount of tear secretion and causing dry eye symptoms.During this process,the expression of an endogenous small molecule,palmitoylethanolamide(PEA),decreased significantly.This study aimed to discuss the role and mechanism of PEA in SD-induced dry eye.Methods:The model of SD was established by the method of using sticks over water.The intensity of sleep deprivation was selected 5d and 1 Od respectively.The PEA content in SD mice tissues was determined by HPLC-MSn method.The solvent group and the PEA-treated group began intraperitoneal injection of control solvent and PEA solution twice a day on SD 6d.After SD 1Od,the dry eye clinical measurement indicators such as tear secretion,corneal sensitivity,OGD and PAS staining were detected.The volume and quality of the lacrimal gland tissue were measured,and frozen,paraffin sections and transmission electron microscope samples were prepared.HE staining was used to evaluate the size of lacrimal gland acinar cells.Oil red O staining was used to detect lipid accumulation in lacrimal gland.Transmission electron microscopy was used to detect the ultrastructure of lacrimal gland acinar cells.The main mechanism of action was discussed with PPAR-?(-/-)and PPAR-a inhibitor MK886.Results:Compared with the control mice,the PEA content in the lacrimal glands of SD 5d and 10d mice decreased significantly,mainly due to the significant decrease in the expression of the synthetic enzyme NAPE-PLD.Administration of exogenous PEA gradient-dependently increased the amount of tear secretion in mice and restored acinar cell volume.PEA can significantly inhibit lacrimal lipid accumulation and improve cell mitochondrial damage caused by lipid accumulation.At the same time,PEA can increase the number of conjunctival goblet cells and increase the amount of tear secretion,thereby reducing corneal sensitivity,reducing corneal barrier damage and improving SD.Dry eye symptoms caused.The above effects of PEA were not observed in PPAR-? knockout mice and after administration of PPAR-? inhibitor MK886.Conclusion:PEA is involved in the pathological changes of lacrimal gland induced by SD and the development of dry eye.PEA can improve a series of dry eye symptoms caused by SD by reducing lipid accumulation in lacrimal gland acinar cells and improving acinar cell function.This process may work through the systemic system rather than being confined to the lacrimal gland.The main pharmacological effects of PEA are mainly mediated by PPAR-? receptors,which may be an effective treatment for relieving dry eye symptoms caused by lack of sleep.