期刊
MOLECULAR NEURODEGENERATION
卷 7, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/1750-1326-7-7
关键词
glutamate receptor 2; retinal degeneration; retinal remodeling; neuritogenesis
资金
- NIH [EY002576, EY015128, EY014800]
- Research to Prevent Blindness
- Signature Immunologics
- Edward N. and Della L. Thome Memorial Foundation
- Moran Eye Center Tiger Team Translational Medicine
- Fight For Sight
- Knights Templar Eye Foundation
- International Retinal Research Foundation
- [5T32 HD07491]
Background: 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. 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. Results: 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. Conclusions: All together, LIRD rapidly triggers GluR2 plasticity, which is a potential mechanism behind functionally phenotypic revisions of retinal neurons and neuritogenesis during retinal degenerations.
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