April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
sGCα1-Deficient Mice: A Novel Murine Model Of Spontaneous Primary Open Angle Glaucoma
Author Affiliations & Notes
  • Emmanuel S. Buys
    Anesthesia, Massachusetts General Hospital, Boston, Massachusetts
  • Sarah Hayton
    Anesthesia, Massachusetts General Hospital, Boston, Massachusetts
  • Alexander Jones
    Ophthalmology, Schepens Eye Research Institute, Boston, Massachusetts
  • Yu-Chieh Ko
    Ophthalmology, Mass Eye & Ear Infirmary, Boston, Massachusetts
  • Meredith Gregory
    Ophthalmology, Schepens Eye Research Institute, Boston, Massachusetts
  • Haiyan Gong
    Ophthalmology, Boston University, Boston, Massachusetts
  • Peter Brouckaert
    Molecular Biomedical Research, Ghent University, VIB, Ghent, Belgium
  • Louis R. Pasquale
    Ophthalmology, Mass Eye & Ear Infirmary, Boston, Massachusetts
  • Kenneth D. Bloch
    Anesthesia, Massachusetts General Hospital, Boston, Massachusetts
  • Bruce Ksander
    Ophthalmology, Schepens Eye Research Institute, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Emmanuel S. Buys, None; Sarah Hayton, None; Alexander Jones, None; Yu-Chieh Ko, None; Meredith Gregory, None; Haiyan Gong, None; Peter Brouckaert, None; Louis R. Pasquale, None; Kenneth D. Bloch, None; Bruce Ksander, None
  • Footnotes
    Support  Harvard Catalyst grant 5 UL1 RR025758-02; Shaffer Fund Grant Project, Glaucoma Research Foundation; MGH ECOR Fromulaic Bridge Funding Support
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 5880. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Emmanuel S. Buys, Sarah Hayton, Alexander Jones, Yu-Chieh Ko, Meredith Gregory, Haiyan Gong, Peter Brouckaert, Louis R. Pasquale, Kenneth D. Bloch, Bruce Ksander; sGCα1-Deficient Mice: A Novel Murine Model Of Spontaneous Primary Open Angle Glaucoma. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5880.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: : Primary open angle glaucoma (POAG) is a common, progressive eye disease that leads to blindness due to the loss of retinal ganglion cells (RGCs) and degeneration of the optic nerve. Elevated intraocular pressure (IOP) is an important risk factor for glaucoma. However, the exact molecular mechanisms that trigger increased IOP and glaucomatous optic neuropathy are incompletely understood. While a few spontaneous murine models of glaucoma exist, none are models of POAG. Impaired nitric oxide (NO)/cGMP signaling has been implicated in the development of glaucoma. This project aims to establish mice lacking the α1 subunit of the NO receptor soluble guanylate cyclase (sGCα1-/- mice) as a spontaneous mouse model for elevated IOP and POAG.

Methods: : IOP was measured serially using a TonoLab-Tonometer in age-matched female WT and sGCα1-/- mice (n=15 and 37 eyes, respectively). Trabecular meshwork in WT and sGCα1-/- was examined by light and transmission electron microscopy. Retinal whole mounts were stained for β III tubulin to visualize RGCs. Axons in optic nerve cross sections were stained with paraphenylenediamine and counted.

Results: : The IOP in sGCα1-/- mice increased significantly with age, from 14±2 mmHg at 19±1 wks to 18±3 mmHg at 37±2 wks (P<0.001). By contrast, the IOP in WT mice remained unchanged: 13±2 mmHg at 20±1 wks and 13±2 mmHg at 39±1 wks. Morphological analysis revealed an open iridocorneal angle in eyes from sGCα1-/- mice with high IOP. β III tubulin staining revealed a loss of RGCs and nerve fibers in retinas of sGCα1-/- mice that coincided with a lower axon count in optic nerves from sGCα1-/- mice than from WT mice (70±12 and 140±16 axons/high powered field, respectively, P<0.01).

Conclusions: : These findings support sGCα1-/- mice as a novel spontaneous model of POAG, providing an important tool for testing strategies that lower or prevent elevated IOP associated with POAG.

Keywords: intraocular pressure • nitric oxide • transgenics/knock-outs 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×