Neural Plasticity Revealed by Light-Induced Photoreceptor Lesions.

The retina has long been assumed to remain in stasis after photoreceptor degeneration effectively deafferents the neural retina (Zrenner, 2002). However, a growing literature reveals the more insidious details of retinal degeneration and evidence of early plasticity. Retinal degenerations typically undergo three phases. Early changes observed in phase one are triggered by photoreceptor stress and include misrouting of rhodopsin to the inner segments of photoreceptors (Milam et al., 1998) followed by rhodopsin delocalization to processes extending down in fascicles projecting into the inner nuclear and ganglion cell layers (Li et al., 1995; Milam et al., 1996). Phase two is characterized by active photoreceptor cell death eventually deafferenting bipolar cell populations and eliminating light mediated signaling to the neural retina. Also observed in phase two is the formation of the Müller cell (MC) seal, entombing or walling off the remnant neural retina from what is left of the retinal pigment epithelium and vascular choroid (Jones et al., 2001; Jones et al., 2003; Marc et al., 2003). Formation of the Müller cell seal is likely due to collapse of distal elements of Müller cells, but is also possibly due to hypertrophic processes. Before completion of phase two, all dendritic elements of bipolar cells have retracted and horizontal cells typically have sent axonal processes into the inner plexiform layer (IPL). (Strettoi and Pignatelli, 2000; Park et al., 2001; Strettoi et al., 2002; Strettoi et al., 2003). The final stage of remodeling, phase three, was originally described in the GHL mouse (Jones et al., 2001), however at the time the extent of remodeling across models and the implications for vision rescue was not appreciated. Subsequent work in naturally occurring and genetic models (Jones et al., 2003) revealed extensive remodeling in response to photoreceptor degeneration. This remodeling involves the evolution of processes from all classes of neurons into fascicles that may run for >100 microns in addition to elaboration of new "tufts" of IPL (microneuromas) that form outside the boundaries of the normal stratification of the IPL. These microneuromas are populated with synaptic contacts corruptive of normal visual processing (Marc et al., 2003). Finally, migration of adult neuronal phenotypes throughout the vertical axis of the retina is observed with all cell classes participating. It is believed that in order to maintain normal gene expression, neurons will sprout processes to seek lost glutamatergic signaling. Failing to achieve synaptic contact may result either in cell death or cellular soma migration to other regions of the retina. Amacrine cells are commonly observed translocating to the ganglion cell layer with ganglion cells also migrating up into the inner nuclear layer. [ABSTRACT FROM AUTHOR]