June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Role of FHOD1, EDNRA and LPAR1 on the intraocular pressure lowering effects of miR-200c.
Author Affiliations & Notes
  • Pedro Gonzalez
    Ophthalmology, Duke University, Durham, North Carolina, United States
  • Megan Parker
    Ophthalmology, Duke University, Durham, North Carolina, United States
  • Coralia C Luna
    Ophthalmology, Duke University, Durham, North Carolina, United States
  • Footnotes
    Commercial Relationships   Pedro Gonzalez, None; Megan Parker, None; Coralia Luna, None
  • Footnotes
    Support   NIH grants EY23287 and EY05722
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 3482. doi:
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      Pedro Gonzalez, Megan Parker, Coralia C Luna; Role of FHOD1, EDNRA and LPAR1 on the intraocular pressure lowering effects of miR-200c.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3482.

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

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Abstract

Purpose : We have previously reported that miR-200c mimic induced strong inhibition of contraction and decreased cell traction forces in human trabecular meshwork (HTM) cells and showed reduction of intraocular pressure (IOP) in rats. Here we investigate the role of some of the miR-200c targets relevant to TM cell contraction (FHOD1, EDNRA and LPAR1) and its effects in rats IOP.

Methods : Primary HTM cells were transduced with adenovirus expressing FHOD1, EDNRA, LPAR1 and null virus and evaluated for changes in gene expression by real time Q-PCR; in protein expression by western blot; and effects on cell contraction by using a three-dimensional collagen gel (1.5 mg/mL COLA1A) contraction assay. Sprague Dawley rats were injected with these viruses in the anterior chamber using a Hamilton syringe and IOP was measured during 15 days using a Tonolab rebound tonometer. Anterior chamber morphology was evaluated by paraffin sections.

Results : HTM cells transduced with EDNRA, FHOD1 and LPAR1 adenoviruses increased gene expression by 2.2 (p 0.016), 124.47 (p 1.15E-06) and 2.6 (p 0.0008) fold respectively. All three genes induced significant contraction of HTM cells on collagen gels compared to controls (15 to 64% less area). Rats injected with FHOD, LPAR or EDNRA showed a slight but significant increase in IOP around days 6 to 12. Morphology of the anterior chamber looks normal after injection of the viruses.

Conclusions : Mir-200c is a post-transcriptional inhibitor of genes relevant to TM cell contraction. FHOD, LPAR and EDNRA are some of the target genes of miR-200c and its individual overexpression increase HTM cell contraction and induce a small increase in IOP confirming that part of the effects of miR-200c are mediated by these genes.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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