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Ji-Jie Pang, Samuel Wu; Multiple Factor-Mediated Retinal Ganglion Cell Death in the DBA/2J Mouse. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2420. doi: https://doi.org/.
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Glaucomatous retinal ganglion cell (GC) death may be associated with high or normal intraocular pressure (IOP) (high- or normal-tension glaucoma) and eyeball expansion (e.g. congenital glaucoma). The mechanisms underlying GC death and common clinical symptoms among variable subtypes of glaucoma are not clear. We investigated contributions of mechanical stress and strain, as well as age, to GC death in DBA/2J mice.
Confocal microscopy, immunoflorescence and complete retrograde-labeling for GC populations are used for this study.
TO-PRO-3-labeled total neurons in the GC layer were negatively related to age (p=0.021), IOP (p=0.132) and eyeball volume (V) (p<0.001), and the GC population was negatively correlated to age (p<0.001) and V (p=0.011). IOP peaked around 10 months of age and reduced thereafter. GC death was more severe in the peripheral retina than the central retina in all mice. In 11-13- month-old D2 mice, GC death was observed in retinas with either or both IOP elevation and eyeball expansion. Early-stage GC death, presented as small patches covering 2-8° of the retina, was mostly found in young mice (<6 months), while the central retina upstream to the small patches remained intact. Late-stage GC death, appearing as widespread GC loss covering 10-360° of the retina, was observed in adult mice (≥6 months). In some large areas surviving GCs showed a low, but even density. Axons from central GCs were arranged near the edge of an axonal bundle.
Multiple factors including eyeball volume, IOP and age may contribute to GC death. GC death is both location- and cell-type specific. In the peripheral retina, the retina and GCs are highly vulnerable to glaucoma and retinal expansion, and the damage there likely represents the initial pathology in the experimental glaucoma. Retinal expansion could be a common pathology in more than one glaucoma phenotype.
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