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Editors Selection IGR 7-2

Examination methods: In-vivo imaging

Comment by James Lindsey on:

21153 Evaluation of the retina and optic nerve in a rat model of chronic glaucoma using in vivo manganese-enhanced magnetic resonance imaging, Chan KC; Fu Q-L; Hui ES et al., Neuroimage, 2008; 40: 1166-1174

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Methods for in-vivo assessment of optic nerve axon loss in experimental models of glaucoma could facilitate basic studies to further clarify mechanisms of glaucomatous damage as well as the development of potential therapeutics. Chan et al. (573) have demonstrated that manganese tracer MRI can detect axon loss in a rat model of glaucoma. Briefly, monocular elevated intraocular pres-sure (IOP) was induced by laser photocoagulation of episcleral and limbal veins. Two or six weeks later, both eyes received injection of manganese chloride, a molecule that is taken up by neurons and transported down axons by fast axonal transport. The animals were then repeatedly imaged using a T1-weighted MRI protocol. They observed a time-dependent increase in image brightness in the optic nerve profiles that was attenuated in nerves from eyes with six weeks of IOP elevation. Histological analysis of optic nerves from a second group of animals that also had induced IOP elevation for six weeks observed approximately 10% loss of myelinated axons. Also of interest were images showing brighter signal in optic axon tissue within the eye than in the optic nerve tissue. In general, the study was well conducted with appropriate controls and normalization protocols. A weakness is that correlation between optic nerve axon loss measured by MRI and histology was not performed. This was because another study had shown that intraocular injection of sufficient manganese to be detected by their imaging method could also cause axon loss.¹ Of broader interest, this limitation excludes use of this method for longitudinal assessments of damage progression. If further investigations overcome this limitation, it would transform this promising approach from an alternative to histological assessment to a much-needed tool for determining the progression rate of optic nerve damage following IOP elevation.

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