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Luis Perez de Sevilla Muller, Allison Sargoy, Allen Rodriguez, Nicholas Brecha; M1 melanopsin ganglion cells are the most injury-resistant ganglion cell subtype following axotomy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):300.
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© ARVO (1962-2015); The Authors (2016-present)
Optic nerve transection (ONT) is a useful tool to simulate axonal injury occurring in human optic neuropathies such as glaucoma, optic nerve stroke and axonal trauma. Previous studies have established that in mouse and rat, ~5% of the RGCs survive for up to a month following ONT. The neurochemical and morphological characteristics of the RGCs that survive for greater than 3 weeks after axotomy were established in this study.
The neurochemistry and morphology of the RGCs that survive for longer than 3 weeks was established using immunohistochemistry. Antibodies used were to RBPMS, a specific marker for RGCs, to neurofilament-M, a general marker for axons and a population of RGCs, and to melanopsin that specifically marks M1 melanopsin ganglion cells.
M1 cells represent 1.7%, 28% and 55% of all surviving RGCs 7-, 14- and 21-days following axotomy, respectively. Although a significant decrease of the M1 cell density was observed in the retina 7 days after the ONT, the density did not decrease further 14- and 21-days post-axotomy. The soma size of the M1 cells remained compared to the control. An increase in the dendritic field size was only observed 7 days post-ONT and then decrease to normal size. The dendritic M1 area coverage was not affected and their dendrites remained in their usual position in the OFF sublamina of the IPL. In addition, displaced M1 cells were the only displaced RGC in the INL to survive following ONT.
These findings demonstrate that M1 cells in the RGC layer and the displaced M1 RGCs in the INL are the most resistant to injury than the other RGC type following nerve injury. The positive identification of the M1 class of ipRGCs as a remarkably injury-resistant ganglion cell subtype offers an exceptional opportunity to explore neuroprotective molecules that could lead to interventions to spare the loss of vision following optic nerve injury.
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