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Glaucoma Dialogue IGR 16-1
Comments
Comment by Jonathan Crowston on:
56225 Glucose-induced temporary visual recovery in primary open-angle glaucoma: a double-blind, randomized study, Casson RJ; Han G; Ebneter A et al., Ophthalmology, 2014; 121: 1203-1211
See also comment(s) by Jeffrey Goldberg • Keith Martin • Robert Casson •This manuscript is of substantial interest, not because it proffers glucose as a potential treatment for glaucoma, but because it provides evidence in further support of the notion that in glaucoma, there exists a subpopulation of retinal ganglion cells that are metabolically challenged and manifest a reversible reduction in function. Although a number of cohort studies have shown a degree of improvement in visual function in glaucoma patients following IOP lowering, this study is novel in demonstrating improvement in visual function through a mechanism distinct to IOP lowering.
This study is novel in demonstrating improvement in visual function through a mechanism distinct to IOP lowering
By giving an intensive regime of glucose drops (50% every five minutes for one hour), Casson and colleagues were able to significantly increase vitreous glucose levels in pseudophakic individuals. This increase in vitreous glucose levels was associated with a significantly improvement of visual acuity and contrast sensitivity in a cohort of glaucoma patients. In a separate in-vitro study published recently in IOVS,1 the same group also showed that glucose rescues cultured retinal ganglion cells from rotenone, a complex-I inhibitor that blocks ATP production through oxidative phosphorylation. Glucose in these studies protected retinal ganglion cells through restoration of ATP through glycolysis and the pentose phosphate pathway.
This sweet study provides much food for thought!
It is interesting to speculate whether the recent description of complex I dysfunction in a glaucoma cohort2 points to the possibility of a parallel scenario in glaucoma, whereby OXPHOS impairment compromises RGC function and that this is overcome by increasing vitreous glucose levels. Further work is clearly needed in order to understand the precise nature of bioenergetics stress in retinal ganglion cells and how this might be overcome to promote neurorecovery. This sweet study provides much food for thought!
References
- Han G, Wood JP, Chidlow G, Mammone T, Casson RJ. Mechanisms of neuroprotection by glucose in rat retinal cell cultures subjected to respiratory inhibition. Invest Ophthalmol Vis Sci 2013;54(12):7567-7577.
- Lee S, Sheck L, Crowston JG, et al. Impaired complex-I-linked respiration and ATP synthesis in primary open-angle glaucoma patient lymphoblasts. Invest Ophthalmol Vis Sci 2012;53(4):2431-2437.
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