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B. Lorber, A. Guidi, K. R. Martin; Intraocular Pressure Elevation Stimulates Successful Regeneration of Retinal Ganglion Cell Axons in vivo After Optic Nerve Crush in Adult Rats. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5218.
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© ARVO (1962-2015); The Authors (2016-present)
Elevation of intraocular pressure (IOP) reduces retinal ganglion cell (RGC) survival in human glaucoma and experimental animal models. We recently showed that IOP elevation enhances RGC neurite outgrowth in culture, an effect mediated by activated retinal glia. We therefore investigated if IOP elevation would also lead to successful RGC axon regeneration after optic nerve crush (ONC) in adult rats in vivo.
Adult Sprague Dawley-rats received (a) unilateral ONC (n=8), (b) IOP elevation using a trabecular laser model (n=8), (c) ONC+IOP elevation (n=7), or were left untreated (n=8). RGC survival (Nr. of βIII-tubulin/NeuN+ RGC) and retinal glia activation (intensity of GFAP labeling) were quantified in retinal sections 14 days later. The number of GAP43+ RGC axons regenerating past the optic nerve lesion site was also assessed.
RGC survival vs. controls was 56±1.7% after ONC (p<0.001) and 87.3±6% after IOP elevation (p<0.05). Combination of ONC+IOP elevation led to survival of 62.4±3.2% RGC vs. untreated controls (p<0.001), a slight, but significant increase in survival vs. ONC alone (p<0.05). Therefore, ONC+IOP elevation did not result in enhanced RGC death over single treatment, as might be expected. ONC slightly increased retinal glia activation vs. controls (8.6±3.8%), whilst retinal glia activation was higher after IOP elevation (20.2±5.2%; p<0.01 vs. controls, p<0.05 vs. ONC). ONC+IOP strongly increased retinal glia activation (38.1±4.2%) over ONC (p<0.001) and IOP elevation (p<0.05). Concurrently, whilst after ONC only few GAP43+ axons grew past the optic nerve lesion site (21.9±9.2), ONC+IOP elevation led to a ~10 fold increase (203.4±24.1; p<0.001) in regenerating GAP43+ axons.
Acute IOP elevation at the time of ONC led to strongly enhanced retinal glia activation compared to ONC alone. This correlated with a strong increase in RGC axon regeneration potential, and also a slight increase in RGC survival over ONC. These results suggest that enhancing retinal glia activation may facilitate neuronal survival and axon regeneration after injury/disease.
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