May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
PDGF and the Rac1 Pathway Modulate Aqueous Humor Outflow and Intraocular Pressure
Author Affiliations & Notes
  • X. Gasull
    Physiology, Medical School, University of Barcelona-IDIBAPS, Barcelona, Spain
  • E. E. Syriani
    Physiology, Medical School, University of Barcelona-IDIBAPS, Barcelona, Spain
  • E. Abad
    Physiology, Medical School, University of Barcelona-IDIBAPS, Barcelona, Spain
  • G. Cuesto
    Physiology, Medical School, University of Barcelona-IDIBAPS, Barcelona, Spain
  • J. Pintor
    Dept. Bioquimica, E.U. Optica, Universidad Complutense de Madrid, Madrid, Spain
  • M. Morales
    Physiology, Medical School, University of Barcelona-IDIBAPS, Barcelona, Spain
  • Footnotes
    Commercial Relationships  X. Gasull, None; E.E. Syriani, None; E. Abad, None; G. Cuesto, None; J. Pintor, None; M. Morales, None.
  • Footnotes
    Support  MEC grants BFU20006-04169/BFI; BFU2006-15047; BFU2005-01572/BFI
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3712. doi:https://doi.org/
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      X. Gasull, E. E. Syriani, E. Abad, G. Cuesto, J. Pintor, M. Morales; PDGF and the Rac1 Pathway Modulate Aqueous Humor Outflow and Intraocular Pressure. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3712. doi: https://doi.org/.

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

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Abstract

Purpose: : It is well known that the small GTPase RhoA modulates the actin cytoskeleton and cellular contractility in the trabecular meshwork (TM). Several substances known to contract the TM, reduce outflow facility, while cellular relaxation is commonly associated to the opposite effect. In this sense, inhibitors of the RhoA pathway are being developed as antiglaucomatous drugs. Here we investigate the role of platelet-derived growth factor, a known activator of the Rac1 pathway, in cell cytoskeleton, outflow facility and intraocular pressure (IOP).

Methods: : Effects of PDGF on actin cytoskeleton, Rac1 and AKT activation were tested in bovine TM cells in culture. Rac1 and AKT/P-AKT activation were assessed by western blot. Trabecular outflow facility was measured in bovine perfused anterior segments. Changes on IOP were measured after topical application in the cornea of rabbit eyes by means of a Tonopen for a period up to 8 hours.

Results: : In TM cells, PDGF (10 ng/ml) activated Rac1 via AKT and induced actin cytoskeleton rearrangement with lamellipodia formation. In this sense, lamellipodia formation in TM cells was prevented by NSC23766, a Rac1 inhibitor and LY29004, a PI3K inhibitor. In perfused anterior segments, PDGF (100 ng/ml) increased trabecular outflow facility by 26%. In vivo, when topically applied to rabbit’s corneas, PDGF induced a 20% decrease in IOP (100 ng/ml). This reduction was concentration-dependent and presented an EC50 value of 2.7 nM.

Conclusions: : PDGF, by activating the Rac1 pathway, induces cytoskeletal changes in TM cells that enhance outflow facility. Decreased IOP after PDGF application is likely due to the facilitation of AH outflow. Rac1 pathway activator appears a positive modulator of outflow facility and an interesting target to decrease IOP after ocular hypertension.

Keywords: cytoskeleton • outflow: trabecular meshwork • intraocular pressure 
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