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Up-regulation of Brain-Derived Neurotrophic Factor Expression by Brimonidine in Rat Retinal Ganglion Cells
Hua Gao, MD, PhD;
Xiaoxi Qiao, MD, PhD;
Louis B. Cantor, MD;
Darrell WuDunn, MD, PhD
Arch Ophthalmol. 2002;120:797-803.
Objectives Brimonidine tartrate ophth, an  2-adrenergic agonist,
is widely used as an antiglaucoma agent for lowering intraocular pressure.
Recent studies suggest that brimonidine may be neuroprotective for retinal
ganglion cells (RGCs) following optic nerve crush injury. Brain-derived neurotrophic
factor (BDNF), a potent neuroprotective factor present in the RGCs, promotes
RGC survival in culture and following optic nerve injury. We tested the hypothesis
that a possible mechanism of brimonidine neuroprotection is through up-regulation
of endogenous BDNF expression in the RGCs.
Methods A single dosage of brimonidine tartrate ophth solution (0.85-34µM)
was injected intravitreally into Sprague-Dawley rat eyes. The fellow eyes
of each animal were injected with balanced salt solution (BSS) and used as
control eyes. To determine BDNF messenger RNA expression, animal eyes were
enucleated and processed for in situ hybridization, or retinas were isolated
and processed for Northern blot analysis using rat BDNF radiolabeled riboprobes.
Results In the control eyes injected with saline, BDNF was present in a minority
of the RGCs. Two days after brimonidine injection, the number of BDNF-positive
RGCs was increased from 55% to 166%, depending on brimonidine concentrations,
when compared with those in the controls. In addition, the BDNF signal intensities
in individual RGCs were elevated 50% in brimonidine-injected eyes compared
with control eyes. Northern blot revealed a 28% increase of BDNF expression
in the brimonidine group compared with the controls (P
<.003). No significant difference was observed in BDNF receptor, trk B, expression between brimonidine, or BSS control groups.
Conclusions A single dose of a low concentration of intravitreal brimonidine is
sufficient to significantly increase endogenous BDNF expression in RGCs. These
results suggest that brimonidine neuroprotection may be mediated through up-regulation
of BDNF in the RGCs. The BDNF should be further investigated regarding its
role in the neuroprotective effects reported with brimonidine.
Clinical Relevance Brimonidine may be (potentially) used clinically as a neuroprotective
agent in optic neuropathy, including glaucoma, and ischemic and traumatic
optic neuropathy.
Department of Ophthalmology, Indiana University School of Medicine,
Indianapolis (Drs Gao, Cantor, and WuDunn), and the Department of Cellular
Biology and Anatomy, Louisiana State University Health Science Center, Shreveport,
La (Dr Qiao).
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