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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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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.
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.
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.
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.
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