July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Sleep deprivation induces dry eye through inhibition of PPARα expression in corneal epithelium
Author Affiliations & Notes
  • Liying Tang
    Eye Institut of Xiamen University, Xiamen, China
  • Zuguo Liu
    Eye Institut of Xiamen University, Xiamen, China
  • Yongxiong Chen
    Eye Institut of Xiamen University, Xiamen, China
  • Footnotes
    Commercial Relationships   Liying Tang, None; Zuguo Liu, None; Yongxiong Chen, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3299. doi:
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      Liying Tang, Zuguo Liu, Yongxiong Chen; Sleep deprivation induces dry eye through inhibition of PPARα expression in corneal epithelium. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3299.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : As nothing has been reported regarding the underlying mechanism account for sleep deprived-dry eye (SDE), we hypothesized that SDE was due to declines in peroxisome proliferator-activated receptor alpha (PPARα) activity, transient receptor potential vanilloid 6 (TRPV6) expression and altered superficial corneal epithelial cell (SCECs) microvilli morphology.

Methods : A PPARα agonist, fenofibrate, and a PPARα inhibitor, MK886 were topically applied to SDE mice established by using a “stick over water” method. Scanning electron microscopy (SEM) evaluated SCECs microvilli morphology in normal and PPARα-/- mice. Quantitative RT-PCR (q), Western blot (WB) or immunostaining evaluated PPARα, carnitine palmitoyl transferase 1α (CPT1α) and TRPV6 expression levels. Hematoxylin & eosin and Oil Red O staining characterized meibomian gland morphology and changes in epithelial lipid deposition, respectively. In corneal epithelial sheets, qRT-PCR, WB and SEM determined the effects of fenofibrate and MK886 on PPARα and TRPV6 expression and SCECs microvilli morphology.

Results : Decreases in PPARα activity were associated with lipid deposition, and declines in CPT1α and TRPV6 expression levels and microvilli morphological changes whereas fenofibrate reversed these effects, However, the meibomian gland was unaffected in SDE mice. Molecular changes induced by SDE in normal mice corneas mimicked those occurring in their PPARα-/-counterpart. Fenofibrate reversed the changes in SCECs microvilli morphological integrity and density of cultured corneal epithelial sheets whereas MK886 attenuated increases in TRPV6 expression accompanying restoration of microvilli morphology.

Conclusions : Our results are consistent with our hypothesis that SDE was accompanied by declines in PPARα activity, TRPV6 expression and altered SCECs microvilli morphology. As this condition was reversed by stimulating PPARα activity with fenofibrate, this transcription factor is a potential drug target to improve therapeutic management of this condition.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

 

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