July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
PPAR-α agonist Fenofibrate Suppressed the formation of ocular surface squamous metaplaisa induced by topical benzalkonium chloride
Author Affiliations & Notes
  • Huan He
    Eye Institute & Affiliated Xiamen Eye Center of Xiamen University, Xiamen, Fujian, China
  • rongrong zong
    Eye Institute & Affiliated Xiamen Eye Center of Xiamen University, Xiamen, Fujian, China
  • Hui He
    Eye Institute & Affiliated Xiamen Eye Center of Xiamen University, Xiamen, Fujian, China
  • Tong Zhou
    Eye Institute & Affiliated Xiamen Eye Center of Xiamen University, Xiamen, Fujian, China
  • yueping zhou
    Eye Institute & Affiliated Xiamen Eye Center of Xiamen University, Xiamen, Fujian, China
  • LIN Zhirong
    Eye Institute & Affiliated Xiamen Eye Center of Xiamen University, Xiamen, Fujian, China
  • Zuguo Liu
    Eye Institute & Affiliated Xiamen Eye Center of Xiamen University, Xiamen, Fujian, China
  • Footnotes
    Commercial Relationships   Huan He, None; rongrong zong, None; Hui He, None; Tong Zhou, None; yueping zhou, None; LIN Zhirong, None; Zuguo Liu, None
  • Footnotes
    Support  NSFC grant 81570816, 81200657 (China)
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3300. doi:
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      Huan He, rongrong zong, Hui He, Tong Zhou, yueping zhou, LIN Zhirong, Zuguo Liu; PPAR-α agonist Fenofibrate Suppressed the formation of ocular surface squamous metaplaisa induced by topical benzalkonium chloride. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3300.

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

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Abstract

Purpose : To investigate the effects and possible mechanisms of a PPAR-α agonist fenofibrate on the formation of ocular surface squamous metaplasia in a mouse dry eye model induced by topical benzalkonium chloride (BAC)

Methods : The eye drops containing fenofibrate were topically administered twice daily within the induction period of 16 days for mouse dry eye by BAC. Mouse were divided to four group according to the topical or intraperitoneal injection: no treatment (Blank group), topical vehicle (Vehicle group), topical fenofibrate (Feno group) or topical fenofibrate plus intraperitoneal injection of MK886, an antagonist of PPAR-α (Feno+MK886 group). The clinical indications of dry eye were evaluated on day (D) 16, including tear break-up time (BUT), tear volume, corneal fluorescein staining and inflammatory index. Global specimens were collected on D16 and the following examinations were performed: histologic investigation, periodic acid-schiff (PAS) assay to detect goblet cells, and immunostaining of cytokeratin 10 (K10), Ki67 on the ocular surface and F4/80 in the cornea. The levels of TNF-α and IL-1β were measured by ELISA assay. CCK-8 assay was performed to evaluate the inhibitory effects of fenofibrate to RAW264.7 cells.

Results : Fenofibrate suppressed the formation of BAC-induced dry eye, presenting with longer BUTs, lower corneal fluorescein staining scores and inflammatory index, while no significant changes in tear volume. Fenofibrate also reduced the severity of abnormal differentiation and proliferation on ocular surface with lower expressions of K10 and Ki67. Fenofibrate also reduced the number of F4/80 positive cells and the levels of TNF-α and IL-1β in the cornea and conjunctiva. In addition, the cell viability of RAW264.7 cells could be significantly inhibited by fenofibrate in a dose-dependent pattern. These effects of fenofibrate could be partially interrupted by MK886.

Conclusions : Topical application of fenofibrate suppressed the formation of BAC-induced dry eye and reduced the severity of ocular surface squamous metaplasia. The effects of fenofibrate might be mediated through PPAR-α signaling pathway and specific inhibition of macrophages. These results revealed the clinical potential of fenofibrate and macrophage might play an important role in ocular surface squamous metaplasia.

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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