Mu Peng-Yue, Chu Chen-Chen, Yu Di, Shao Yan, Zhao Shao-Zhen
Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China.
Int J Ophthalmol. 2020 Jun 18;13(6):860-869. doi: 10.18240/ijo.2020.06.02. eCollection 2020.
To investigate the regulatory roles of the members of the peroxisome proliferator-activated receptor (PPAR) family in lacrimal gland dysfunction under conditions of desiccating stress or diabetes.
Quantitative polymerase chain reaction (qPCR) was used to examine the expression of PPARs in the cornea, conjunctiva, meibomian gland, and lacrimal gland in adult rats. The rats were divided into 3 groups: a control group, dry eye group, and diabetic group. The phenol red threads test, tear film break-up time (BUT) test and fluorescein staining were carried out to evaluate the development of dry eye. Based on bioinformatics research, qPCR was used to examine the expression level of PPARγ, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), sirtuin 1 (Sirt1), myeloid differentiation factor 88 (MyD88) and transforming growth factor-β (TGF-β) in the lacrimal glands.
PPARα and PPARβ/δ were mainly expressed in the conjunctiva and the lacrimal gland, respectively. However, PPARγ was expressed in both the conjunctiva and lacrimal gland, at much higher levels than those measured for PPARα and PPARβ/δ. Dry eye rats and diabetic rats both showed decreased tear secretion, shortened BUT, and increased corneal staining. Significant changes in gene expression were observed compared with the control group. In the lacrimal glands of dry eye rats and diabetic rats, expression of PPARγ decreased (<0.05), expression of Sirt1 also decreased (<0.01), whereas expression of TNF-α, IL-1β, IL-6, MyD88, and TGF-β increased (<0.05).
Among PPARs, PPARγ might play a dominant role in the regulation of metabolic- and inflammatory-signaling pathways on the ocular surfaces and in lacrimal glands. Down-regulation of PPARγ is highly relevant to lacrimal gland dysfunction under desiccating-stress and diabetic conditions. PPARγ, thus, is a potential therapeutic target in the treatment of environment- or diabetes-induced dry eye diseases.
研究过氧化物酶体增殖物激活受体（PPAR）家族成员在干燥应激或糖尿病条件下泪腺功能障碍中的调节作用。
采用定量聚合酶链反应（qPCR）检测成年大鼠角膜、结膜、睑板腺和泪腺中PPARs的表达。将大鼠分为3组：对照组、干眼组和糖尿病组。进行酚红棉线试验、泪膜破裂时间（BUT）试验和荧光素染色以评估干眼的发展。基于生物信息学研究，使用qPCR检测泪腺中PPARγ、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、沉默调节蛋白1（Sirt1）、髓样分化因子88（MyD88）和转化生长因子-β（TGF-β）的表达水平。
PPARα和PPARβ/δ分别主要在结膜和泪腺中表达。然而，PPARγ在结膜和泪腺中均有表达，且表达水平远高于PPARα和PPARβ/δ。干眼大鼠和糖尿病大鼠均表现出泪液分泌减少、BUT缩短和角膜染色增加。与对照组相比，基因表达有显著变化。在干眼大鼠和糖尿病大鼠的泪腺中，PPARγ的表达降低（<0.05），Sirt1的表达也降低（<0.01），而TNF-α、IL-1β、IL-6、MyD88和TGF-β的表达增加（<0.05）。
在PPARs中，PPARγ可能在眼表和泪腺的代谢及炎症信号通路调节中起主导作用。PPARγ的下调与干燥应激和糖尿病条件下的泪腺功能障碍高度相关。因此，PPARγ是治疗环境或糖尿病引起的干眼疾病的潜在治疗靶点。
