Rapid glutamate receptor 2 trafficking during retinal degeneration

Adult albino Balb/C mice were exposed to intense light for 24 h to induce light-induced retinal degeneration (LIRD). We found that prior to the onset of photoreceptor loss, protein levels of GluR2 and related trafficking proteins, including glutamate receptor-interacting protein 1 (GRIP1) and postsynaptic density protein 95 (PSD-95), were rapidly increased. LIRD triggered neuritogenesis in photoreceptor survival regions, where GluR2 and its trafficking proteins were expressed in the anomalous dendrites. Immunoprecipitation analysis showed interaction between KIF3A and GRIP1 as well as PSD-95, suggesting that KIF3A may mediate transport of GluR2 and its trafficking proteins to the novel dendrites. However, in areas of photoreceptor loss, GluR2 along with its trafficking proteins nearly vanished in retracted retinal neurites.All together, LIRD rapidly triggers GluR2 plasticity, which is a potential mechanism behind functionally phenotypic revisions of retinal neurons and neuritogenesis during retinal degenerations.Retinal degenerations (RD), such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), are progressive disorders initiated by photoreceptor stress and are accelerated by photoreceptor death, which effectively deafferents the inner retina and evolves into formal retinal remodeling [1-3]. Thus, retinal remodeling proceeds through three phases: 1, photoreceptor stress; 2, photoreceptor death and 3, complex neural remodeling [3]. Two of the major hallmarks of retinal remodeling are growth of novel neurites and functional reprogramming of existing retinal neurons [1-8]. Pathogenic neuronal reprogramming and de novo neuritogenesis are not isolated to retinal tissues, as pathological revision also occurs in neurodegenerative diseases such as epilepsy [9] and Alzheimer's disease [10]. Retinal remodeling limits the effectiveness of vision rescue strategies including photoreceptor- and retinal pigment epithelium (RPE)-directed therapies [4,6,7,11,12