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B.P. Buckingham, D.M. Inman, P.J. Horner; RGC Cell Death or Axon Transport Defect in a Mouse Model of Glaucoma . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3803.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Glaucoma is a group of devastating eye diseases that are characterized by progressive and permanent loss of vision. A prevailing hypothesis is that raised intraocular pressure leads to retinal ganglion cell (RGC) death. One study injected retrograde tracers into the superior colliculus of the DBA/2J mouse, a strain that spontaneously develops glaucomatous symptoms, and showed that labeled RGCs decreased from ∼5,000 cells/mm2 at 3 months of age to ∼1,000 cells/mm2 at 18 months (IOVS 2003; 44:5151–5162). Our study aims to explore the possibility that retrograde labeling may not accurately document the functional state or time of death of the RGC soma. Methods: We examined RGC location and number in DBA/2J mouse retina using the neuron–specific DNA binding protein present in mature neurons, NeuN (Neuronal Nuclei). Retinal whole mounts from 8 time points (2 to 18 months) were labeled with anti–NeuN antibody. The ganglion cell layers of these retinas were then analyzed using unbiased stereology. Results: Mean cellular density across all retinas was 4,094 –+ 347 cells/mm2; there was no significant difference in density between young and old DBA/2J. Conclusions: RGC death following glaucomatous symptoms is based primarily on the observation of decreased retrograde transport of tracers injected into RGC projection areas of the brain or the observation of a thinning ganglion cell layer. Our data suggest that RGCs in glaucomatous retina may be dying much later than expected or possibly not at all. The presence of axonal transport deficits might explain discrepancies in RGC numbers obtained via retrograde labeling as opposed to immunohistochemical markers of RGCs. The quantification of NeuN–labeled ganglion cells is now being compared to other RGC markers and a functional assessment of retrograde transport and axonal pathology is ongoing.
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