Inhibition Of Ceramide De Novo Synthesis Ameliorates Meibomian Gland Dysfunction Induced By SCD1 Deficiency

ObjectiveMeibomian gland dysfunction(MGD)is a chronic diffuse meibomian gland dysfunction characterized by terminal duct obstruction or changes in the quality or quantity of lipid secreted by the glands.It is the cause of many ocular surface diseases.The defecticy of stearoyl-CoA desaturase 1(SCD1)is considered to be one of the causes of MGD,but related research is lacking.This study aims to show the specific histopathological changes of the meibomian glands in SCD1 deficient mice,and to reveal the internal mechanism of SCD1 deficient inducing MGD.MethodsThe SCD1 knockout mouse model was established,and the histopathological changes of the meibomian glands in different developmental stages of knockout mice were observed by slit lamp,stereomicroscope,HE staining,and oil red O staining.The 2 week-old knockout mice were further subjected to immunofluorescence staining and transmission electron microscopy to observe their changes in keratinization,apoptosis,inflammation,differentiation and other changes.High performance liquid phase mass spectrometry was used to analyze the lipid changes in the meibomian glands of knockout mice.The SCD1 inhibitor A939 was injected intraperitoneally to establish a mouse model of meibomian gland dysfunction.Set up solvent control group,L-cyclo(ceramide de novo synthesis rate-limiting enzyme SPT inhibitor)group,and A939+L-cyclo group.Use slit lamp,stereo microscope,HE staining,oil red O staining,immunofluorescence,etc.to observe the mouse meibomian glands,neutral lipid expression,keratinization,inflammation,apoptosis and related protein expression to clarify the nerves The role of ceramide in the process of SCD1 deletion inducing MGD.ResultsThe ducts of the meibomian glands of 2 weeks old knockout mice are obviously blocked,and the glands begin to appear missing.And as they age,the glands are missing to disappear,and the lipid accumulation in the duct mouth also disappears.There are MGD-related pathological changes in the meibomian glands of old mice,and the expression of SCD1 is significantly reduced.Compared with wild-type mice,the meibomian glands of SCD1 knockout mice gradually shrank to loss with age.The meibomian glands of knockout mice at 2 weeks of age showed obvious pathological manifestations such as abnormal differentiation,keratinization,apoptosis,inflammatory cell infiltration,mitochondrial vacuolation,and increased ceramide content.In wild-type mice,intraperitoneal injection of SCD1 inhibitor A939 showed similar pathological manifestations of MGD as SCD1 knockout mice,while administration of L-cyclo at the same time could prevent A939-induced MGD.ConclusionAge-related MGD may be related to the down-regulation of SCD1;SCD1 deletion cause severe meibomian gland dysfunction;inhibition of ceramide de novo synthesis can block MGD caused by SCD1 deficiency.