Koc University Center for Translational Medicine Research, Istanbul, Turkey.
Department of Ophthalmology, Koç University Medical School, Istanbul, Turkey.
Curr Eye Res. 2020 Jan;45(1):72-80. doi: 10.1080/02713683.2019.1656750. Epub 2019 Aug 27.
: Type 2 Diabetes mellitus (DM) is a major health problem and its ocular complications like orbital infections, cataract and diabetic retinopathy cause blindness. Meibomian gland (MG) dysfunction and dry eye disease are also important ocular complications of type 2 DM but not enough research has been conducted on these complications. Our hypothesis suggests type 2 DM can alter significant gene expressions of MG. In our study, MGs of leptin-deficient spontaneous diabetic and non-diabetic mice were extracted, and gene expression profiles were analyzed with microarray technology.: Mice were divided into two groups; nine Lep spontaneous diabetic mice as type 2 DM group and nine non-diabetic Balb/c mice as controls. Blood glucose levels, tearfilm break-up time and fluorescein scores were measured in both two groups for 12 weeks. MGs were dissected and RNAs were isolated for microarray gene expression analysis. We filtered probes with standard deviation of more than 0.1 and we used 40452 of 45281 probes for processing. We performed fold change analysis and identified which genes are affected, and we analyzed the impact of genes on proteins, pathways and gene ontologies by using various databases.: We 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 the other hand, IL-33, cholecystokinin, plasminogen activator, IL-1 and serine peptidase inhibitor genes down-regulated significantly. Also, we have seen a significant decrease in WNT signaling and pentose phosphate pathways-related genes.: Our data show 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 MGs were negatively affected by type-2 DM.
2 型糖尿病（DM）是一个主要的健康问题，其眼部并发症，如眼眶感染、白内障和糖尿病视网膜病变导致失明。睑板腺（MG）功能障碍和干眼症也是 2 型 DM 的重要眼部并发症，但对这些并发症的研究还不够。我们的假设表明，2 型糖尿病可能会改变 MG 的重要基因表达。在我们的研究中，提取了瘦素缺陷自发性糖尿病和非糖尿病小鼠的 MG，并使用微阵列技术分析了基因表达谱。
将小鼠分为两组；九只 Lep 自发性糖尿病小鼠为 2 型糖尿病组，九只非糖尿病 Balb/c 小鼠为对照组。两组小鼠均测量血糖水平、泪膜破裂时间和荧光素评分 12 周。分离 MG 并分离 RNA 进行微阵列基因表达分析。我们过滤了标准差大于 0.1 的探针，并用 45281 个探针中的 40452 个进行处理。我们进行了倍数变化分析，确定了哪些基因受到影响，并使用各种数据库分析了基因对蛋白质、途径和基因本体的影响。
与非糖尿病小鼠相比，我们观察到 2 型糖尿病小鼠中 172 个上调基因和 118 个下调基因。有趣的是，DM 时胶原蛋白 I、整合素β I 结合蛋白 I、丙酮酸脱氢酶激酶、TNF 受体基因表达上调；另一方面，IL-33、胆囊收缩素、纤溶酶原激活物、IL-1 和丝氨酸肽酶抑制剂基因显著下调。此外，我们还观察到 WNT 信号和戊糖磷酸途径相关基因的显著减少。
我们的数据表明，这些基因表达的变化是由 2 型糖尿病的内分泌和免疫机制引起的，导致 MG 上皮细胞的内稳态紊乱。凋亡和炎症相关基因的表达增加及其对相关途径的影响证明，MG 受到 2 型糖尿病的负面影响。
