The mechanism of axonal degeneration after perikaryal excitotoxic injury to the retina

We investigated 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, which display delayed Wallerian degeneration. 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. Furthermore, RGC somal loss was greater in Wld(s) rats. Microglial response in the anterior visual pathway to injury was attenuated in the Wld(s) rats with lymphocytic infiltration that was relatively reduced; however, immunostaining for major histocompatibility complex class II antigens (OX6) was more pronounced in Wld(s) rats. 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.

► Perikaryal excitotoxic retinal ganglion cell injury causes Wallerian degeneration. ► Degeneration is delayed by up to 4 weeks in Wld(s) rats. ► Microglial response in the optic nerve was attenuated in the Wld(s) rats. ► These data support the notion of a labile, soma-derived axonal survival factor.