May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Investigation of in vivo Effects of Glutamate Modulating Stratages in Glaucoma–Related Models of Retinal Ganglion Cell Apoptosis
Author Affiliations & Notes
  • L. Guo
    Institute of Ophthalmology, London, United Kingdom
    Glaucoma & Retinal Neuron Degeneration Group, Pathology,
  • T.E. Salt
    Institute of Ophthalmology, London, United Kingdom
    Visual Science,
  • A. Maass
    Institute of Ophthalmology, London, United Kingdom
    Glaucoma & Retinal Neuron Degeneration Group, Pathology,
  • V. Luong
    Institute of Ophthalmology, London, United Kingdom
    Visual Science,
  • S.E. Moss
    Institute of Ophthalmology, London, United Kingdom
    Cell Biology,
  • F.W. Fitzke
    Institute of Ophthalmology, London, United Kingdom
    Visual Science,
  • M.F. Cordeiro
    Institute of Ophthalmology, London, United Kingdom
    Glaucoma & Retinal Neuron Degeneration Group, Pathology,
    The Glaucoma Research Group, The Western Eye Hospital St Mary's Hospital NHS Trust, London, United Kingdom
  • Footnotes
    Commercial Relationships  L. Guo, None; T.E. Salt, None; A. Maass, None; V. Luong, None; S.E. Moss, None; F.W. Fitzke, None; M.F. Cordeiro, None.
  • Footnotes
    Support  Wellcome Trust GR063658 HIGHWIRE EXLINK_ID="47:5:3921:1" VALUE="GR063658" TYPEGUESS="GEN" /HIGHWIRE , GR076947 HIGHWIRE EXLINK_ID="47:5:3921:2" VALUE="GR076947" TYPEGUESS="GEN" /HIGHWIRE , TFC Frost, Lilly
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 3921. doi:
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      L. Guo, T.E. Salt, A. Maass, V. Luong, S.E. Moss, F.W. Fitzke, M.F. Cordeiro; Investigation of in vivo Effects of Glutamate Modulating Stratages in Glaucoma–Related Models of Retinal Ganglion Cell Apoptosis . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3921.

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

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Abstract

Purpose: : To assess neuroprotective effects of different glutamate modulation strategies, with the NMDA receptor antagonists (MK801 and Ifenprodil), and a metabotropic glutamate receptor agonist (LY354740), using glaucoma–related in vivo rat models.

Methods: : Retinal ganglion cell (RGC) apoptosis was induced in Dark Agouti (DA) rats (n=94) by staurosporine (SSP) treatment. Single agents of MK801, ifenprodil and LY354740 or combined applications of MK801 and LY354740 were administrated intravitreally at different doses. Eyes were imaged in vivo using our recently established technique, and results confirmed histologically. The most effective combined therapy regimen of MK801 and LY354740 was then assessed in a chronic ocular hypertension (OHT) rat model (n=16) with application at 0, 1 and 2 weeks after OHT surgery, and effects assessed as described before.

Results: : All strategies of glutamate modulation reduced SSP–induced–RGC apoptosis compared to control, in a dose–dependent manner by MK801 (R2=0.8863), ifenprodil (R2=0.4587) and LY354740 (R2=0.9094), with EC50s of 0.074, 0.0138 and 19 nmol respectively. The most effective combination dose of MK801/LY354740 was 0.06/20nmol (p<0.05), and the optimal timing of this was at 0 weeks after OHT surgery (p<0.05).

Conclusions: : Our novel SSP–model was validated as a useful tool for screening neuroprotective strategies in vivo. Group II mGluR modulation may be a useful treatment strategy for preventing RGC death. Combination therapy optimised to limit neurotoxic effects of MK801 may be an effective neuroprotective approach in retinal degenerative disease. Furthermore, strategies minimising secondary RGC degeneration effects may be most useful in glaucoma.

Keywords: neuroprotection • apoptosis/cell death • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) 
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