Rapid glutamate receptor 2 trafficking during retinal degeneration

Yanhua Lin,J Scott Lauritzen,Bryan W Jones,W Drew Ferrell,Félix R Vazquéz-Chona,Aihua Liu,Robert E Marc

doi:10.1186/1750-1326-7-7

Yanhua Lin, J Scott Lauritzen + Show 5 more

Open Access

https://doi.org/10.1186/1750-1326-7-7

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Journal: Molecular Neurodegeneration	Publication Date: Feb 10, 2012
Citations: 35	License type: cc-by

Affiliation: University of Utah

Abstract

BackgroundRetinal 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 in particular. However, the molecular events associated with retinal remodeling remain largely unknown. Given our prior evidence 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.ResultsAdult 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.ConclusionsAll together, LIRD rapidly triggers GluR2 plasticity, which is a potential mechanism behind functionally phenotypic revisions of retinal neurons and neuritogenesis during retinal degenerations.

Highlights

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 in particular
light-induced retinal degeneration (LIRD) increases glutamate receptor 2 (GluR2) expression prior to obvious photoreceptor loss LIRD led to dramatic photoreceptors loss by post-light exposure day 7 (Figure 1A), demonstrating that LIRD is a “fast degenerating” animal model of retinal degeneration [32]
GluR2 immunostaining of control tissues revealed GluR2-immunoreactive puncta aggregating in the outer plexiform layer (OPL) with more GluR2-immunoreactive puncta found throughout the OFF and ON sublamina (Figure 1E)

Summary

Introduction

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 in particular. 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 [1,2,3]. Two of the major hallmarks of retinal remodeling are growth of novel neurites and functional reprogramming of existing retinal neurons [1,2,3,4,5,6,7,8]. Better understanding of the mechanisms underlying retinal remodeling will improve the outcomes of genetic, molecular, cellular and bionic rescues

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