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Editors Selection IGR 15-4

Optic Nerve Head: Axonal transport after IOP elevation

Comment by James Morgan on:

19647 Axonal transport and cytoskeletal changes in the laminar regions after elevated intraocular pressure, Balaratnasingam C; Morgan WH; Bass L et al., Investigative Ophthalmology and Visual Science, 2007; 48: 3632-3644

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Balaratnasingam et al. (867) study the changes in axonal transport and cytoskeletal elements in porcine optic nerve heads. Their hypothesis is that axonal transport and neurofilament structure are disrupted following elevation in intraocular pressure. To test this, they used a model in which the IOP was elevated acutely to 40-45 mmHg for six hours. The authors acknowledge the limitations of this approach when trying to understand the changes that occur in a chronic disease such as glaucoma. The principle findings of the study are that anterograde axonal transport (as measured using a fluorescent tracer, RITC delivered by intravitreal injection, where it is taken up by retinal ganglion cells) is reduced in the laminar and retrolaminar parts of the optic nerve head following IOP elevation. Immunohistochemical labelling for the neurofilaments NFH And NFM, including the phosphorylated form of NNFH was also reduced in the eyes with elevated pressure. The novel aspects of the study are the degree to which parameters were controlled at the time of the IOP elevation. The IOP was monitored continuously during the experiment as well as the CSF pressure- these measurements are technically difficult and not practical in chronic models of IOP elevation. A potential confounder in the experiment is that the elevation in IOP may directly have affected uptake of the RITC tracer; this does not appear to be the case since levels of labelling in the control and hypertensive eyes were not significantly different in the prelaminar part of the optic nerve.

Controlled models for the study of IOP on optic nerve head function are needed

It is also important to note that the optic nerves were fixed after euthanasia; it would have been preferable for the animals to be euthanised by perfusion fixation since postmortem changes can be rapid and it cannot be safely assumed that these would occur in the same rate in both the control and experimental eyes. Given the robust nature of the model, it should be possible, in future to allow greater time for axon transport. It should also be possible to analyse changes in retrograde transport, following tracer injections to visual centres such as the LGN or Superior colliculus.

The study highlights the importance of using controlled models for the study of IOP on optic nerve head function. While the primate has been a valuable model of glaucoma its use has declined in recent years because of cost and local issues related to the use of animals in research. The search for other models of optic nerve head disease in models with features that are similar to the human will continue to add to the debate concerning the pathophysiology of retinal ganglion cell loss in glaucoma.

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