Rapid glutamate receptor 2 trafficking during retinal degeneration.
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.
Department of Ophthalmology, John A, Moran Eye Center, University of Utah School of Medicine, 65 Mario Capecchi Drive, Salt Lake City, UT 84132, USA.
Yanhua
Y
Lin
Bryan W
BW
Jones
Aihua
A
Liu
Félix R
FR
Vazquéz-Chona
J Scott
JS
Lauritzen
W Drew
WD
Ferrell
Robert E
RE
Marc
D000818:Animals; D003712:Dendrites / Q000378:metabolism; D005260:Female; D008027:Light / Q000009:adverse effects; D051379:Mice; D008807:Mice, Inbred BALB C; D016501:Neurites / Q000378:metabolism; D010786:Photoreceptor Cells / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012160:Retina / Q000378:metabolism; D012162:Retinal Degeneration / Q000378:metabolism*; D055351:Retinal Neurons / Q000378:metabolism
D018091:Receptors, AMPA; C104722:glutamate receptor ionotropic, AMPA 2