September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
RhoA-mediated contractility of the trabecular meshwork regulates intraocular pressure in the early but not in the late fibrotic phase of Primary Open Angle Glaucoma
Author Affiliations & Notes
  • Lisa J Hill
    Neurotrauma Research Group, University of Birmingham, Birmingham, United Kingdom
  • Ben Mead
    Neurotrauma Research Group, University of Birmingham, Birmingham, United Kingdom
  • Felicity de Cogan
    Neurotrauma Research Group, University of Birmingham, Birmingham, United Kingdom
  • Elena Feinstein
    Research Division, Quark Pharmaceuticals, Ness Ziona, Israel
  • Zubair Ahmed
    Neurotrauma Research Group, University of Birmingham, Birmingham, United Kingdom
  • Richard J Blanch
    Neurotrauma Research Group, University of Birmingham, Birmingham, United Kingdom
  • Peter Morgan-Warren
    Neurotrauma Research Group, University of Birmingham, Birmingham, United Kingdom
  • Martin Berry
    Neurotrauma Research Group, University of Birmingham, Birmingham, United Kingdom
  • Ann Logan
    Neurotrauma Research Group, University of Birmingham, Birmingham, United Kingdom
  • Footnotes
    Commercial Relationships   Lisa Hill, None; Ben Mead, None; Felicity de Cogan, None; Elena Feinstein, None; Zubair Ahmed, None; Richard Blanch, None; Peter Morgan-Warren, None; Martin Berry, None; Ann Logan, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4690. doi:
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      Lisa J Hill, Ben Mead, Felicity de Cogan, Elena Feinstein, Zubair Ahmed, Richard J Blanch, Peter Morgan-Warren, Martin Berry, Ann Logan; RhoA-mediated contractility of the trabecular meshwork regulates intraocular pressure in the early but not in the late fibrotic phase of Primary Open Angle Glaucoma. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4690.

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

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Abstract

Purpose : To investigate the role of RhoA and the effects of inhibiting RhoA in modulating trabecular meshwork (TM) contractility, intraocular pressure (IOP) and retinal ganglion cell (RGC) death in a rodent model of open angle glaucoma.

Methods : Twice weekly intracameral injections of Transforming Growth Factor β (TGFβ) were used to induce TM fibrosis and ocular hypertension in rats over 35d. Test and control groups of rats were co-injected with siRhoA or siEGFP, respectively, and IOP was measured. Rats were euthanized at either 7d or 35d. Fibronectin, laminin, αSMA, MLC-p and Brn3a+ RGC were quantified.

Results : IOP was increased after bi-weekly intravitreal TGFβ together with siEGFP treatment, with a transient IOP peak measured at 7d followed by a sustained rise in IOP between 14d and 35d. By contrast, when TGFβ treatment was combined with siRhoA the acute IOP rise was absent. Higher levels of fibronectin and laminin were observed in the TM at 35d compared to 7d, irrespective of siRNA treatment. However, siRhoA lowered the αSMA and MLCp levels at 7d. A 30% loss of Brn3a+ RGC occurred in TGFβ treated eyes at 35d, irrespective of siRNA treatment.

Conclusions : RhoA-mediated TGF-b-induced TM contraction causes the acute rise in IOP, an adverse early stage response that is potentially amenable to therapeutic blockade with siRhoA. By contrast, TGF-b-induced TM fibrosis that is responsible for the chronic, sustained rise in IOP and, ultimately, progressive RGC loss is RhoA-indpendent.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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