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Editors Selection IGR 21-2

Experimental Glaucoma: RGC dendritic shrinkage after optic nerve crush

Comment by Chris Leung on:

50386 Retinal ganglion cell morphology after optic nerve crush and experimental glaucoma, Kalesnykas G; Oglesby EN; Zack DJ et al., Investigative Ophthalmology and Visual Science, 2012; 53: 3847-3857

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The Thy-1 YFP transgenic mice engineered by Feng and associates provide an efficient model to examine the dendritic and axonal structures of retinal ganglion cells (RGCs).¹ Kalesnykas and colleagues conducted an elegant study investigating the change in dendritic structure in the Thy-1 YFP mice after optic nerve crush and elevation of intraocular pressure induced by intracameral injection of microbeads.² Although dendritic measurements were not obtained longitudinally from the same RGCs, a large number of RGCs were analyzed and compared cross-sectionally at different time points between the control and optic nerve injury groups (589 RGCs in the optic-nerve crush study and 736 RGCs in the experimental glaucoma study). After optic-nerve crush, significant decreases in RGC axons and dendritic complexity were evident. Unexpectedly, in the experimental glaucoma group, RGCs had greater total dendritic outgrowth and longer dendritic process length at three weeks (but not at six weeks) in spite of significant axon loss (17% and 31% loss at three and six weeks, respectively). The authors proposed that there might be a phase in which RGCs expand their dendrites in glaucoma and suggested further investigation to validate the finding.

It is worth noting that while the numbers of RGCs in the control and glaucoma groups for comparison were similar at each study time points in the glaucoma study, it is not revealed whether the proportion of large and small RGCs were in the same way comparable. If small RGCs are preferentially damaged in the early phase of the experimental glaucoma (notably, the IOP was up to ~36mmHg at day one for the three-week glaucoma group), a higher proportion of large RGCs in the three-week glaucoma group would have contributed to the apparent increase in dendritic complexity. At a later time point (the six-week glaucoma group), reduction in dendritic complexity was noticed albeit statistically insignificant.

Examining the same RGCs longitudinally with in-vivo imaging techniques can provide a more reliable and definitive approach to decipher the change in dendritic complexity after optic-nerve injury. Previous studies have shown the possibility of measuring the rate of dendritic shrinkage of individual RGCs after optic-nerve crush and acute elevation of IOP.^2,3 Although challenges remain to generate a glaucoma model with mildly to moderately elevated IOP lasting for a sufficiently long period of time with a clear optical media, it is promising that in-vivo analysis of dendritic arborization would provide new insights into the neurobiology of RGC degeneration and neuroprotection in glaucoma.

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