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Comment by Keith Martin 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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The neurodegenerative cascade in glaucoma includes several somatic and axonal components involving changes in intracellular calcium or calcium dysregulation. This is so of the pathogenesis in most other age-related neurodegenerative disorders (Mattson, 2007). Thus, a major directive of neuroprotective strategies is to identify either pharmacological or dietary interventions that counter calcium dysregulation. In their study, Ma et al. (2009) test whether systemic (intraperitoneal) application of the α₂-adrenergic agonist brimonidine protects rat retinal ganglion cell (RGC) neurons from injury due to transient (60-second) unilateral clamping of the optic nerve. The sole outcome measure is quantification of RGCs labeled retrogradely from fluorogold injections into the superior colliculus four weeks after crush and a daily treatment regimen. They describe a modest increase (21%) in the number of labeled RGCs in the test eye of the treatment group compared to untreated.
Several points bear discussion. The outcome measure is not an indicator of RGC survival per se, which is a common misconception. Rather it is a measure of dynein-mediated active axonal transport, which is the basis for fluorogold movement from the colliculus to the retina (see Buckingham et al., 2008).

The outcome measure is a measure of dynein-mediated active axonal transport, which is the basis for fluorogold movement from the colliculus to the retina

In the treatment group, the number of labeled RGCs was not only higher in the crush eye, but also moderately in the na�ve eye (the median was 8% higher in the brimonidine group). While this reduced the net improvement with treatment to about 13% (p = 0.02), it could indicate that the observed effect of systemic brimonidine treatment actually represents a modest increase in the efficacy of axonal transport. Dong et al.(2008) demonstrated that brimonidine reduces NMDA-mediated calcium influx by lowering intracellular cAMP. Decreased calcium could lead to lower rates of calpain-mediated microtubule degradation. But, since lower cAMP would tend to impede tubulin reorganization (Liu & Brady, 2004), the overall enhancement would be incremental.

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