July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Hsa-let-7c-3p downregulates lens epithelial mesenchymal transition by inhibiting CDH11 in TGFβ induced anterior subcapsular cataract in retinitis pigmentosa
Author Affiliations & Notes
  • Min Hou
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, Guang Dong, China
  • Furong Luo
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, Guang Dong, China
  • Xuan Bao
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, Guang Dong, China
  • Mingxing Wu
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, Guang Dong, China
    Cataract, Zhongshan Ophthalmic Center, Guangzhou, Guangdong, China
  • Footnotes
    Commercial Relationships   Min Hou, None; Furong Luo, None; Xuan Bao, None; Mingxing Wu, None
  • Footnotes
    Support  NSFC Grant 81470615
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5650. doi:
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      Min Hou, Furong Luo, Xuan Bao, Mingxing Wu; Hsa-let-7c-3p downregulates lens epithelial mesenchymal transition by inhibiting CDH11 in TGFβ induced anterior subcapsular cataract in retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5650.

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

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Abstract

Purpose : Anterior subcapsular cataract (ASC) associated with Retinitis pigmentosa (RP) dramatically impairs the restricted visual field of the low-vision population. The role of the microRNA in ASC formation remains unknown. Here we investigate how let-7c-3p regulates the TGF-β induced lens epithelial mesenchymal transition (EMT) in ASC associated with RP.

Methods : TGF-β levels in the AH were detected by multiplex bead immunoassay in the aqueous humor and microRNAs expression profiles were analyzed by microarrays and validated by RT-PCR. Phenotypic alterations were analyzed by Western blot analysis and immunofluorecence staining in in anterior specimens and LECs. Target validation was performed by a luciferase reporter assay to identify the putative target of let-7c-3p and target gene expression was blocked using specific small interfering RNA (siRNA).

Results : TGF-β levels in the AH and TGFβ type II receptor was significantly increased in the ASC patients. LECs significantly downregulated the hsa-let-7c-3p both in the ASC associated with RP and in TGF-β2 induced EMT in vitro. Overexpression of hsa-let-7c-3p inhibits the LECs proliferation, migration and downregulated the levels of EMT markers in TGFβ2-induced EMT of LECs. Besides, inhibition of endogenous hsa-let-7c-3p decreased the levels of EMT factors, respectively. TargetScan predicted four target sequences in the 3′ untranslated region (UTR) of the OB-Cadherin (CDH11) mRNA and direct targeting of this 3′ UTR by hsa-let-7c-3p was demonstrated using a luciferase assay. Immunofluorescence validated increased CDH11 expression in ASC in RP patients. Silencing of CDH11 using a specific siRNA had identical reversed effects on EMT in vitro.

Conclusions : The study demostrated the regulatory role of hsa-let-7c-3p in downregulating CDH11 expression and the downstream TGFβ signaling, which eventually alleviates fibrogenisis. Our study adds to the growing list of miRNAs and target genes found to definitely participate in lens fibrosis.

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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