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Editors Selection IGR 9-3

Basic Research: High IOP rodent model

Comment by John Danias on:

25153 The microbead occlusion model: a paradigm for induced ocular hypertension in rats and mice, Sappington RM; Carlson BJ; Crish SD et al., Investigative Ophthalmology and Visual Science, 2010; 51: 207-216

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Sappington et al. (115) describe a new induced, high IOP, rodent model of glaucoma. The authors have developed this model by injecting polysterene microspheres in the anterior chamber of both rats and mice. IOP increases in both animal species by about 30% from pre-injection values and lasts for a short period of time (approximately two to three weeks) but can be extended up to periods of at least five to six weeks by a reinjection at 14 days. Sappington et al. report that IOP elevation of this magnitude can cause measurable (albeit small, ~15-25%) axonal loss in both animal species.

The work described in this paper is exceptional. The authors have made a real effort to characterize the effect of microbead injection on IOP and have tested multiple parameters including bead size, and injection volume. Although there are some methodological problems (for example, injection seems to be performed centrally in the cornea which may affect accurate determination of IOP, IOP is measured by tonopen in mice etc), the results are convincing. In fact other labs have replicated some of these data (personal communication) confirming the usefulness of this model for raising IOP. What is not as convincing is the axonal loss at least at the early time-point (~5 weeks) the authors decided to look at. Fixation of the optic nerves was performed only with paraformaldehyde which is not ideal for morphometric studies. The images provided as examples (which presumably are the best possible) do not show much degeneration. Although the use of automated routines to count all myelin sheaths in ON sections is positive, small differences in the location of sections along the length of the Ons could potentially account for the differences seen. It is thus imperative that the ON damage aspect of this model be further evaluated.

A reproducible, easily replicated rodent model of IOP elevation that can be used to study its effects on the retina and optic nerve

The establishment of a new experimental model is always a challenging proposition. It needs to simulate human pathology as closely as possible, but also provide 'handles' that can be manipulated to meaningfully test hypotheses about the disease. The authors have clearly moved the field forward by establishing the microbead injection model. Although certain aspects of this model need further study (and possibly standardization) the first step has clearly been made. We at least now have a reproducible, easily replicated rodent model of IOP elevation that can be used to study its effects on the retina and optic nerve. Whether rodent Ons are equally susceptible to damage caused by IOP elevation compared with primate eyes is still an open issue but at least we now have a way to test it. The authors should be really applauded for this work.

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