Effects of type 2 diabetes mellitus on gene expression profile of meibomian glands in mice

Abstract

AbstractPurposeDiabetes mellitus (DM) is a major health problem and its complications cause blindness. Meibomian gland dysfunction and dry eye disease are also important ocular complications related with DM. According to our hypothesis, DM can exhibit significant altered gene expression in meibomian glands. To test our hypothesis, meibomian glands of leptin deficient spontaneous diabetic and non‐diabetic mice were extracted and gene expression profiles were analyzed with microarray.MethodsNine Lepob/ob spontaneous diabetic mice and nine non‐diabetic Balb/c mice (control group) were used. Blood glucose levels, tearfilm break‐up time and fluorescein scores were measured for 12 weeks. Meibomian glands were dissected and RNAs were isolated for microarray gene expression analysis. Probes with standard deviation more than 0.1 were filtered and used 40 452 of 45 281 probes for processing. Fold change analysis were performed and identified for affected genes, and impact of genes on proteins, pathways and gene ontologies were analyzed by using various databases.ResultsWe observed 172 up‐regulated and 118 down‐regulated genes in type‐2 diabetic mice when compared to non‐diabetic mice. Interestingly, expression of collagen type‐I, integrin beta‐I binding protein‐I, pyruvate dehydrogenase kinase, TNF receptor genes up‐regulated with DM; on other hand, IL‐33, cholecystokinin, plasminogen activator, IL‐1 and serine peptidase inhibitor genes down‐regulated significantly. Also, we have seen significant decrease in WNT signaling and pentose phosphate pathways related genes.ConclusionOur data shows these changes in gene expression caused by endocrine and immune mechanisms of type‐2 DM which result disrupted homeostasis of epithelial cells of MG. Increased expressions of apoptosis and inflammation related genes and their effects on related pathways have proven that meibomian glands were negatively affected from type‐2 DM.