Rod bipolar cells dysfunction occurs before ganglion cells loss in excitotoxin-damaged mouse retina.

ABSTRACT: Progressive degeneration of retinal ganglion cells (RGCs) will cause a blinding disease. Most of the study is focusing on the RGCs itself. In this study, we demonstrate a decline of the presynaptic rod bipolar cells (RBCs) response precedes RGCs loss and a decrease of protein kinase C? (PKC?) protein expression in RBCs dendrites, using whole-cell voltage-clamp, electroretinography (ERG) measurements, immunostaining and co-immunoprecipitation. We present evidence showing that N-methyl D-aspartate receptor subtype 2B (NR2B)/protein interacting with C kinase 1 (PICK1)-dependent degradation of PKC? protein in RBCs contributes to RBCs functional loss. Mechanistically, NR2B forms a complex with PKC? and PICK1 to promote the degradation of PKC? in a phosphorylation- and proteasome-dependent manner. Similar deficits in PKC? expression and response sensitivity were observed in acute ocular hypertension and optic never crush models. In conclusion, we find that three separate experimental models of neurodegeneration, often used to specifically target RGCs, disrupt RBCs function prior to the loss of RGCs. Our findings provide useful information for developing new diagnostic tools and treatments for retinal ganglion cells degeneration disease.

SUBMITTER: Shen Y 

PROVIDER: S-EPMC6885518 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature