Retinal glymphatic system: an explanation for transient retinal layer volume changes?

Abstract

This scientific commentary refers to ‘Retinal inner nuclear layer volume reflects response to immunotherapy in multiple sclerosis’, by Knier et al. (doi:10.1093/brain/aww219) . A recent article in Brain by Gelfand et al. (2012) on the inner nuclear layer (INL) of the retina in multiple sclerosis triggered a lively exchange of Letters to the Editor. With the advent of optical coherence tomography (OCT), a forgotten autopsy observation was restored to the top of the research agenda in multiple sclerosis. Over 150 years ago, severe atrophy of the retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) was shown to be associated with only subtle changes in the INL whilst the outer retinal layers were completely preserved (Muller, 1857). Although Heinrich Muller was cautious in interpreting potential INL changes, he was more convinced about the existence of secondary (retrograde) axonal degeneration. ‘Die sogenannten Korner erschienen etwas kornig, doch war mir sehr zweifelhaft, ob dies als pathologische Veranderung anzusprechen sei, da man Aehnliches auch sonst zu Gesicht bekommt.’ This case was discussed on pages 92–98 and the citation taken from page 93 (Muller, 1857). For the contemporary translation it is important to refer back to the terminology of the time. There were three ‘Kornerschichten’ that correspond to the present day: ‘ganglion cell layer’, ‘inner nuclear layer’ and ‘outer nuclear layer’. Muller was not able to see the GCL and his comment is on the next nuclear layer, the INL: ‘The so called nuclei seemed more grainy, but I am rather doubtful if this should be interpreted as a (specific) pathological finding as one can see similar features in other situations’. Subsequent histological studies of the macaque monkey eye following experimental lesions to the afferent visual pathway provided evidence for retrograde trans-synaptic degeneration reaching the GCL with associated changes in the …