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Editors Selection IGR 18-1

Basic Science: Neuroprotective Effects of Glucose

Comment by Derek Welsbie on:

61531 Effect of subconjunctival glucose on retinal ganglion cell survival in experimental retinal ischaemia and contrast sensitivity in human glaucoma, Shibeeb O; Chidlow G; Han G et al., Clinical and Experimental Ophthalmology, 2016; 44: 24-32

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Robert Casson and his colleagues in Adelaide have a series of papers showing that increasing intraocular glucose decreases retinal ganglion cell (RGC) death in rodent models of optic neuropathy, including glaucoma.^1-3 Moreover, they have some evidence to suggest that elevated glucose levels might actually improve the function of injured, but not yet dead, human RGCs, a concept known as neurorecovery.⁴ In this most recent study from his group, Shibeeb et al. test whether similar neuroprotection and neurorecovery could be achieved with subconjunctival administration of a highly-concentrated glucose solution. In the first part, rats were given a large subconjunctival bolus of 50% glucose, enough to elevate the vitreous levels of glucose nearly two-fold. One hour after the challenge, severe ocular hypoxia was produced, an injury well-known to trigger RGC cell death. In this model, known as ischemia/reperfusion, the rat anterior chamber was cannulated and the intraocular pressure raised well above the systolic blood pressure for one hour, totally occluding blood flow. One week later, the number of surviving RGCs in the retina was measured using conventional RGC markers and by counting optic nerve axons. As expected, control-treated eyes demonstrated the RGC loss typical of the model. In contrast, eyes pretreated with subconjunctival glucose had only half the RGC death (although there was significant variability). While exciting, it remains to be seen whether the protection is sustained (beyond one week), whether a similar effect would be seen in the setting of a treatment paradigm (as opposed to prevention) and whether the rescued RGCs remain functional, all hallmarks of a successful neuroprotective strategy.

In the second part, using a cross-over design, Shibeeb and coauthors identified five pseudophakic primary open-angle glaucoma patients and randomized them to receive subconjunctival glucose or an osmolarity-matched saline control. Of note, the injection was accompanied by marked pain, precluding the authors from considering similar formulations in the future. Before and two hours after treatment, contrast sensitivity was measured over a range of spatial frequencies. Consistent with their previous work, the authors found that glucose-treated eyes actually had improved contrast sensitivity. However, before concluding that glucose is promoting neurorecovery, it will be important to show that the RGC is the cellular substrate of the effect as many other cells and structures could be affected by the sudden increase in glucose. Nonetheless, this paper builds upon a body of work which has repeatedly shown that elevated glucose levels influence the RGC response to hypoxic injury, through a mechanism that is surely the goal of current research.

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