We (Yanhua Lin, myself, Aihua Liu, Félix R. Vazquéz-Chona, J. Scott Lauritzen, W. Drew Ferrell and Robert E. Marc) just published another paper on rapid changes in glutamate receptor 2 trafficking during retinal degeneration.
Retinal degenerations, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), are characterized by photoreceptor loss and anomalous remodeling of the surviving retina that corrupts visual processing and poses a barrier to late-stage therapeutic interventions. We’ve been particularly interested in some of the early molecular events associated with retinal degenerative diseases and retinal remodeling as they are largely unknown. Given our prior evidence here and here of ionotropic glutamate receptor (iGluR) reprogramming in retinal degenerations, we hypothesized that the edited glutamate receptor 2 (GluR2) subunit and its trafficking may be modulated in retinal degenerations.
It turns out this was correct. In light induced models of retinal degeneration, iGluR2 plasticity is rapidly altered 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), rapidly increased. We also saw extensive neuritogenesis in photoreceptor survival regions, where GluR2 and its trafficking proteins were expressed in the anomalous dendrites.