RRC ID 36001
Author Jiang H, Wang X, Zhang H, Chang Y, Feng M, Wu S.
Title Loss-of-function mutation of serine racemase attenuates excitotoxicity by intravitreal injection of N-methyl-D-aspartate.
Journal J Neurochem
Abstract Convincing data demonstrate that D-serine, a racemized product of serine racemase (SR), contributes to neurotoxicity. Furthermore, a line of evidence suggests that SR/D-serine contributes to retinal neurodegeneration in a diabetic retinopathy rat model and diabetic retinopathy patients. However, the connection between SR/D-serine and retinal neurodegeneration remains unclear. Herein, we report that intravitreal injection of N-methyl-D-aspartate (NMDA) induces excitotoxicity in rodent retina; this retinal neurodegeneration was attenuated in retina carrying a loss-of-function of mutation in Srr, the gene for SR, termed Srr(ochre269). Under the condition of NMDA injection, either posterior pole or middle - but not peripheral - retina from Srr(ochre269) mice was found to retain more retinal ganglion cells (RGC) than the counterpart from w/t (RGCs were identified with retrograde labeling). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining further demonstrated reduced RGC apoptosis from Srr(ochre269) compared to w/t mice under the condition of NMDA injection. Collectively, our studies demonstrate a pivotal role of SR/D-serine in retinal neurotoxicity. We demonstrated that loss-of-function mutation of the gene encoding serine racemase significantly attenuates excitotoxicity in retina; excitotoxicity accounts for retinal ganglion cell (RGC) demise in diabetic retinopathy (DR). We think that our findings deepen the current knowledge of the mechanisms of RGC degeneration.
Volume 136(1)
Pages 186-93
Published 2016-1-1
DOI 10.1111/jnc.13400
PMID 26485193
MeSH Animals Excitatory Amino Acid Agonists / administration & dosage Excitatory Amino Acid Agonists / toxicity* Female Intravitreal Injections Male Mice Mice, Inbred C57BL Mice, Transgenic Mutation / genetics* N-Methylaspartate / administration & dosage N-Methylaspartate / toxicity* Racemases and Epimerases / genetics* Retina / drug effects Retina / enzymology Retinal Ganglion Cells / drug effects* Retinal Ganglion Cells / enzymology*
IF 4.066
Times Cited 9
Mice RBRCGD000099