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Robert J. Casson, Glyn Chidlow, Natalie Bull, John Wood, Keith Martin; The Mechanism of Axonal Degeneration after Perikaryal Excitotoxic Injury to the Retina. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2980.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the mechanism of secondary axonal degeneration after perikaryal excitotoxic injury to retinal ganglion cells (RGCs) by comparing pathological responses in wild-type rats and Wld(s) rats with delayed Wallerian degeneration.
Adult wild-type Sprague Dawley (SD) and adult homozygous Wlds transgenic rats were used. Perikaryal excitotoxic injury was induced by a 5 microliter intravitreal injection of 8 mM N-methyl-D-aspartate (NMDA). To assess the effect of the Wlds protein on the time course of RGC degeneration after excitotoxic injury, 32 SD and 32 Wlds rats were randomly assigned to one of three groups, which were killed at 1 week (SD n=10; Wlds n=10), 2 weeks (SD n=10; Wlds n =10) and 4 weeks (SD n =12; Wlds n =12) after injury. Surviving RGCs in excitotoxic-injured retinas were quantified at each time point using immunohistochemical labeling of the common quantifiable RGC marker NeuN. Wholemount retinas and sections from the optic nerve and optic tract were immunolabelled for cytoskeletal proteins (SMI-32, NF-L, beta 3-tubulin), and axonal counts were performed. Immunological tissue responses were assessed with immunolabelling for microglial (Iba1) and MHC Class II (OX6) antigens.
After perikaryal excitotoxic RGC injury, both types of rats exhibited a spatio-temporal pattern of axonal cytoskeletal degeneration consistent with Wallerian degeneration, which was delayed by up to 4 weeks in Wld(s) rats (Fig. 1), but RGC somal loss was greater in Wld(s) rats. The microglial response in the anterior visual pathway was attenuated in the Wld(s) rats; however, immunostaining for MHC Class II antigens was more pronounced in Wld(s) rats, but lymphocytic infiltration was relatively reduced.
These data indicate that perikaryal excitotoxic RGC injury causes a secondary Wallerian axonal degeneration, and support the notion of a labile, soma-derived axonal survival factor.
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