論文 - 詳細
| RRC ID | 36001 |
|---|---|
| 著者 | Jiang H, Wang X, Zhang H, Chang Y, Feng M, Wu S. |
| タイトル | Loss-of-function mutation of serine racemase attenuates excitotoxicity by intravitreal injection of N-methyl-D-aspartate. |
| ジャーナル | 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. |
| 巻・号 | 136(1) |
| ページ | 186-93 |
| 公開日 | 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 |
| 引用数 | 9 |
| WOS 分野 | NEUROSCIENCES BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRCGD000099 |