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Editors Selection IGR 9-4

Medical Treatment: Continuous delivery of brimonidine and GC survival

Comment by Robert Nickells on:

28228 Brimonidine prevents axonal and somatic degeneration of retinal ganglion cell neurons, Lambert WS; Ruiz L; Crish SD et al., Molecular Neurodegeneration, 2011; 6: 4

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The selective β2-adrenergic receptor agonist, brimonidine, may have an important dual role in the treatment of glaucomatous neurodegeneration. Used as a topical eye-drop, brimonidine inhibits the production of aqueous humor and facilitates a decrease in intraocular pressure (IOP). This effect alone provides an essential ingredient to attenuating retinal ganglion cell degeneration, but it may not be the only effect that brimonidine has.

Brimonidine was more effective (than control) at attenuating the degeneration of cell bodies and axons

A variety of studies have clearly documented that this drug can also interact with, and protect, retinal ganglion cells in a pressureindependent manner. Additionally, recent clinical trial data support an enhanced preservation of visual function in low-tension glaucoma patients receiving brimonidine, versus timolol, even though IOPs between groups were similarly controlled.¹ The study by Lambert et al. (331) documents the effects of continuous delivery of brimonidine on ganglion cell soma and axonal survival and function in a rat model of glaucoma. In this series of experiments, brimonidine was delivered subcutaneously from a small osmotic mini-pump to rats with elevated IOP in one eye. At the end of eight weeks, the retinas were evaluated for ganglion cell soma densities, and the optic nerves were evaluated for axon survival. In both metrics, brimonidine was more effective at attenuating the degeneration of cell bodies and axons relative to untreated or vehicle-treated control groups. Importantly, however, this group also showed a significant effect of brimonidine on improving anterograde axonplasmic transport, suggesting that the action of this drug may influence aspects of the entire retinal projection of the visual pathway.

Overall this elegant study complements an earlier report in a different rat glaucoma model, which showed that retrograde transport and neuronal soma survival were also preserved by weekly intraperitoneal injections of brimonidine.²

The effectiveness of brimonidine may be most effective when the visual pathway is intact

Interestingly, however, this same study reported that brimonidine did not attenuate ganglion cell atrophy, while a second study now indicates that it is ineffective in retinal explants, where ganglion cells have been severed from their target neurons.³ Collectively, these data may indicate that the effectiveness of brimonidine may be most effective when the visual pathway is intact.

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