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Glaucoma Dialogue IGR 11-1

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Comment by David Calkins on:

22579 Effect of brimonidine on retinal ganglion cell survival in an optic nerve crush model, Ma K; Xu L; Zhang H et al., American Journal of Ophthalmology, 2009; 147: 326-331

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In the broadest sense, neuroprotection refers to the capacity to prevent or limit neuronal injury. Currently, the only proven clinical neuroprotectant in glaucoma management acts indirectly by unclear mechanisms: reduction of the intraocular pressure. Direct neuroprotection of retinal ganglion cells (RGCs) would be a highly desirable adjunct to our limited therapeutic armamentarium. Remarkably, some of the currently available ocular hypotensive drugs are reported to have direct neuroprotective effects on the RGCs, against a variety of insults. Of these, brimonidine has received the most attention (with most studies coming out of the Irvine labs). Betaxolol is a close second, but presently unfashionable.
Brimonidine is an α2-agonist which has been shown experimentally to attenuate RGC death in a number of in vitro and in vivo models.¹ The mechanism of action is unclear, but may involve anti-apoptotic effects related to alpha-2-adrenoreceptor activation1 or BDNF upregulation² or modulation of the NMDA receptor.³

Ma et al. report that intraperitoneal brimonidine attenuates RGC death in a rat model of optic nerve crush. The paper is not novel. Yoles, Schwartz and Wheeler published almost identical findings a decade ago.⁴ Both groups used retrograde labeling of RGC somata, by Fluorogold (FG) injection into the superior colliculus, to measure survival. In both studies, the FG was injected some time after the crush, with the idea that only surviving axons would transmit the dye to their respective RGC somata. In the earlier report, the authors attempted to distinguish acute degeneration from secondary degeneration; no attempt was made by the authors of the recent paper. The difference in FG labeling was small but reached statistical significance. Whether or not brimonidine is a clinically significant direct neuroprotectant requires further study. Results from the Low-pressure Glaucoma Treatment Study,⁵ if they become available, may help answer this question.

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