July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Keratocytes promote corneal neovascularization through MMP13 induced by PPARα-inhibition
Author Affiliations & Notes
  • Xue Wang
    Aier school of ophthalmology, Central South University, Changsha, China
    Eye Institute of Xiamen University, Medical College of Xiamen University, Xiamen, China
  • Liying Tang
    Eye Institute of Xiamen University, Medical College of Xiamen University, Xiamen, China
  • Wensheng Li
    Aier school of ophthalmology, Central South University, Changsha, China
    Shanghai Aier Eye Hospital, Shanghai, China
  • Yongxiong Chen
    Eye Institute of Xiamen University, Medical College of Xiamen University, Xiamen, China
  • Footnotes
    Commercial Relationships   Xue Wang, None; Liying Tang, None; Wensheng Li, None; Yongxiong Chen, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 954. doi:https://doi.org/
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      Xue Wang, Liying Tang, Wensheng Li, Yongxiong Chen; Keratocytes promote corneal neovascularization through MMP13 induced by PPARα-inhibition. Invest. Ophthalmol. Vis. Sci. 2019;60(9):954. doi: https://doi.org/.

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

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Abstract

Purpose : The previous study has reported that keratocytes (KCs) promoted corneal neovascularization (CNV) by degrading and remodeling the extracellular matrix and creating corneal stroma space. It was achieved through the promotion of matrix metalloproteinase 13 (MMP13) production induced by upregulation of VEGF receptor (r)3 expression. This study aimed to investigate the mechanism by which KCs upregulated the expression of MMP13 and VEGFr3 and promoted the CNV.

Methods : The CNV models were established by alkali burn, and divided into three groups such as normal control, PPARα agonist (200uM fenofibrate) and vehicle control (0.1%DMSO) group. The expression of VEGFr3, MMP13 and PPARα by normal and alkali-burned mice corneas was determined via quantitative (q)RT-PCR and Western Bolt analysis. The CNV was observed under a slit lamp microscope and evaluated via immunohistochemistry. Lipid accumulation was examinated by oil red O staining. The cells that expressed PPARα in the cornea were determined via immunohistochemistry and in situ hybridization. The KCs were treated with 20uM fenofibrate or 0.01%DMSO at 24 hours and the effects of PPARα on VEGFr3 and MMP13 expression in KCs were determined via qRT-PCR and Western Bolt analysis. At the same time, PPARα knockout (PPARα-/-) CNV and KCs models were established to testify that PPARα-/- could promote the VEGFr3 and MMP13 expression.

Results : The progress of CNV was positively correlated with the expression of MMP13 and VEGFr3, however, negatively correlated with the expression of PPARα. Lipid accumulation in the corneal stroma was negatively correlated with the expression of PPARα. PPARα was expressed in epithelial, stroma, endothelial cells in the normal cornea, however, markedly decreased in cornea after alkali burns, which indicated the CNV was related to the PPARα-inhibition. The local application of fenofibrate could promote PPARα expression, and inhibite the VEGFr3 and MMP13 expression and the CNV, which is opposite with the results shown in PPARα-/- CNV models. The PPARα activation could downregulate the VEGFr3 and MMP13 expression in the KCs, which could be upregulated in the PPARα-/- KCs.

Conclusions : KCs could promote the expression of VEGFr3 and MMP13 and the formation of CNV through PPARα-inhibition.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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