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Editors Selection IGR 11-2
Anatomical Structures: ONH change in healthy volunteers
Comment by George Lambrou on:
46230 Mapping of the disease locus and identification of ADAMTS10 as a candidate gene in a canine model of primary open angle Glaucoma, Kuchtey J; Olson LM; Rinkoski T et al., PLoS Genetics, 2011; 7: e1001306
Facing death, not all retinal ganglion cells are equal ! This has been a matter of speculation for decades but, so far, the evidence was mainly based on histologic specimens, showing changes in densities of various cell morphological types, and it was impossible to distinguish changes due to disappearance of specific cell types, from 'morphing' of a cell type into another, e.g. by dendritic or cell body size shrinkage.
This may be about to change: In their IOVS paper, Leung et al. (599) describe the prospective (for up to six months) observation of individual RGCs in live, non-anesthetized transgenic mice expressing a fluorescent protein, using a CSLO-based non-invasive imaging technique. Although similar approaches have been described in the past, less than 1% of the cells are fluorescent in this specific mouse strain, which limits superimposition of fluorescent structures, and therefore identification of specific cells in subsequent fundus images taken weeks apart. By submitting such mice to a gentle optic nerve crush, the authors have studied the survival of different subpopulations of RGCs in a well-established model of RGC degeneration. Morphometric cluster analysis of 125 RGCs (from 16 retinas) has led the authors to classify the cells in six types (called 'groups 1-6'), based on eight morphological parameters. The induction of neurodegeneration by the crush resulted in morphological changes and, in particular, dendritic shrinkage. This is followed often ‐ but not always ‐ by axonal and eventually cell body loss. Only in rare instances was axonal Wallerian degeneration observed (< 2.4%).
The delayed neurodegeneration implies a potential therapeutic window to restore axonal and dendritic structure after optic nerve injury
Not all cell types were equally prone to degeneration: Group-4 RGCs (characterized by larger bodies, wider dendritic fields, longer dendrites, thinner axons and located farther away from the optic disc) seemed to survive significantly longer; RGCs, with smaller dendritic fields and located nearer the optic disc had a higher rate of dendritic shrinkage. In general, cells with larger dendritic fields, longer total dendritic branch length and a more distal location from the optic disc had a higher probability of survival at 120 days. These observations provide new insights into the mechanisms of neuronal damage following optic nerve injury, while the delayed degeneration implies a potential therapeutic window to restore axonal and dendritic structure. Overall, observations from this novel non-invasive technique create a new paradigm for research into neuroprotection and neurodegeneration.
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