Liying Tang1, Xue Wang1, Jieli Wu1, San Ming Li1, Zhaoqiang Zhang1, Sangang Wu2, Ting Su1, Zhirong Lin1,3, Xueting Chen1, Xulin Liao1, Ting Bai1, Yan Qiu1, Peter Sol Reinach4, Wei Li1,3,5, Yongxiong Chen1, Zuguo Liu1,3,5. 1. Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Medical College, Xiamen University, Xiamen, Fujian, China. 2. Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China. 3. Xiamen University Affiliated Xiamen Eye Center, Xiamen, Fujian, China. 4. Wenzhou Medical University, Wenzhou, Zhejiang, China. 5. The Affiliated Xiang'an Hospital of Xiamen University, Xiamen, Fujian, China.
Abstract
Purpose: To determine if sleep deprivation induces dry eye through altering peroxisome proliferator-activated receptor alpha (PPARα) expression in mice. Methods: The "stick over water" sleep deprivation-induced dry eye (SDE) model evaluated PPARα involvement in inducing this condition. Scanning electron microscopy (SEM) examined microvilli morphology in superficial corneal epithelial cells (SCECs) in SDE and PPARα-/- mice. Quantitative RT-PCR (qRT-PCR) and Western blot (WB) or immunostaining evaluated PPARα, carnitine palmitoyl transferase 1α (CPT1α), and transient receptor potential vanilloid 6 (TRPV6) expression levels and Ezrin phosphorylation status. Hematoxylin-eosin and Oil Red O staining characterized meibomian gland morphology and corneal lipid accumulation, respectively. Phenol red cotton threads measured tear production. In cultured corneal epithelial sheets, qRT-PCR, WB, and SEM determined the individual effects of fenofibrate and MK886 (PPARα agonist and antagonist, respectively) on PPARα, TRPV6 expression, and SCEC microvilli morphology. Results: Corneal epithelial lipid accumulation, microvilli morphologic changes, and decreased tear production were associated with marked declines in PPARα, CPT1α, and TRPV6 expression levels as well as Ezrin phosphorylation status, whereas meibomian glands were unaltered in SDE mice. These effects of SDE mice mimicked those in their nonstressed PPARα-/-counterpart. Topical application of fenofibrate reversed these effects in SDE corneas. In cultured corneal epithelial sheets, fenofibrate increased PPARα and TRPV6 gene and protein expression levels and restored microvilli morphology, whereas MK886 attenuated these changes. Conclusions: Sleep deprivation induces dry eye through abnormal SCEC microvilli morphology, which is caused by sequential downregulation of PPARα, TRPV6 expression, and Ezrin phosphorylation status in mice.
Purpose: To determine if sleep deprivation induces dry eye through altering peroxisome proliferator-activated receptor alpha (PPARα) expression in mice. Methods: The "stick over water" sleep deprivation-induced dry eye (SDE) model evaluated PPARα involvement in inducing this condition. Scanning electron microscopy (SEM) examined microvilli morphology in superficial corneal epithelial cells (SCECs) in SDE and PPARα-/- mice. Quantitative RT-PCR (qRT-PCR) and Western blot (WB) or immunostaining evaluated PPARα, carnitine palmitoyl transferase 1α (CPT1α), and transient receptor potential vanilloid 6 (TRPV6) expression levels and Ezrin phosphorylation status. Hematoxylin-eosin and Oil Red O staining characterized meibomian gland morphology and corneal lipid accumulation, respectively. Phenol red cotton threads measured tear production. In cultured corneal epithelial sheets, qRT-PCR, WB, and SEM determined the individual effects of fenofibrate and MK886 (PPARα agonist and antagonist, respectively) on PPARα, TRPV6 expression, and SCEC microvilli morphology. Results: Corneal epithelial lipid accumulation, microvilli morphologic changes, and decreased tear production were associated with marked declines in PPARα, CPT1α, and TRPV6 expression levels as well as Ezrin phosphorylation status, whereas meibomian glands were unaltered in SDE mice. These effects of SDE mice mimicked those in their nonstressed PPARα-/-counterpart. Topical application of fenofibrate reversed these effects in SDE corneas. In cultured corneal epithelial sheets, fenofibrate increased PPARα and TRPV6 gene and protein expression levels and restored microvilli morphology, whereas MK886 attenuated these changes. Conclusions: Sleep deprivation induces dry eye through abnormal SCEC microvilli morphology, which is caused by sequential downregulation of PPARα, TRPV6 expression, and Ezrin phosphorylation status in mice.
Authors: Paulina Escandon; Brenda Vasini; Amy E Whelchel; Sarah E Nicholas; H Greg Matlock; Jian-Xing Ma; Dimitrios Karamichos Journal: Exp Eye Res Date: 2021-05-16 Impact factor: 3.770
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