April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Brimonidine Attenuates Axonal Transport Deficits in a Laser Model of High-Pressure Glaucoma
Author Affiliations & Notes
  • W. S. Lambert
    Vanderbilt Eye Institute, Vanderbilt University Med Ctr, Nashville, Tennessee
  • L. Ruiz
    Biological Sciences, Allergan, Inc, Irvine, California
  • S. D. Crish
    Vanderbilt Eye Institute, Vanderbilt University Med Ctr, Nashville, Tennessee
  • L. A. Wheeler
    Biological Sciences, Allergan, Inc, Irvine, California
  • D. J. Calkins
    Vanderbilt Eye Institute, Vanderbilt University Med Ctr, Nashville, Tennessee
  • Footnotes
    Commercial Relationships  W.S. Lambert, Allergan, Inc., F; L. Ruiz, Allergan, Inc., E; S.D. Crish, Allergan, Inc., F; L.A. Wheeler, Allergan, Inc., E; D.J. Calkins, Allergan, Inc., F.
  • Footnotes
    Support  Allergan, Inc. Discovery Research Grant (DJC)
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3184. doi:https://doi.org/
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    • Get Citation

      W. S. Lambert, L. Ruiz, S. D. Crish, L. A. Wheeler, D. J. Calkins; Brimonidine Attenuates Axonal Transport Deficits in a Laser Model of High-Pressure Glaucoma. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3184. doi: https://doi.org/.

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

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Abstract

Purpose: : Brimonidine’s use as a treatment for ocular hypertension and glaucoma is due to its ability to decrease aqueous humor production. Independent of its IOP lowering properties, brimonidine is also neuroprotective to RGCs in various in vitro and in vivo models of neurodegeneration. Recent studies indicate that axon specific mechanisms, including axonal transport deficits, play a major role in the pathology of glaucoma. Therefore, we examined brimonidine’s effect on axonal transport to the superior colliculus (SC) in a laser model of high-pressure glaucoma.

Methods: : Unilateral IOP elevation was induced in Sprague Dawley rats by argon laser treatment of the episcleral veins. Brimonidine (1mg/kg) or vehicle was delivered systemically beginning at the time of laser treatment and continuing for 3 weeks or 2 months. Rats received fluorescent cholera toxin subunit b (CTB) via intraocular injection 2 days prior to sacrifice, and CTB transport was quantified in coronal sections through perfusion fixed midbrains containing SC. RGCs and CTB uptake by RGCs were quantified in perfusion fixed retinas by counting phosphorylated neurofilament-heavy (SMI31)+ and CTB+ cells. A naïve group (no laser treatment and no drug or vehicle) was also included.

Results: : Brimonidine increased CTB transport to the SC 186% compared to vehicle (77.1% vs. 26.9% intact transport) at the three week time point, while an 105% increase was observed after two months (69.2% vs. 33.7%). Intact transport in naive rats averaged 94%. As expected RGC number was increased in brimonidine treated eyes at both time points compared to vehicle.

Conclusions: : Brimonidine treatment significantly improved axonal transport to the SC. As transport deficits to and from the SC are relevant to disease progression, brimonidine’s ability to preserve axonal transport suggest its neuroprotective effects are pertinent not only at the cell body, but throughout the entire retinal projection.

Keywords: neuroprotection • ganglion cells • superior colliculus/optic tectum 
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