Sigma 1 受体有助于星形胶质细胞介导的视网膜神经节细胞保护。
Sigma 1 Receptor Contributes to Astrocyte-Mediated Retinal Ganglion Cell Protection.
机构信息
Department of Ophthalmology, Medical College of Georgia at Augusta University, Augusta, Georgia, United States.
Culver Vision Discovery Institute, Augusta, Georgia, United States.
出版信息
Invest Ophthalmol Vis Sci. 2022 Feb 1;63(2):1. doi: 10.1167/iovs.63.2.1.
PURPOSE
Sigma 1 receptor (S1R) is expressed in retinal ganglion cells (RGCs) and astrocytes, and its activation is neuroprotective. We evaluated the contribution of S1R within optic nerve head astrocytes (ONHAs) to growth and survival of RGCs in vitro.
METHODS
Wild-type (WT) RGCs and WT or S1R knockout (S1R KO) ONHAs were cocultured for 2, 4, or 7 days. Total and maximal neurite length, neurite root, and extremity counts were measured. Cell death was measured using a TUNEL assay. Signal transducer and activator of transcription 3 phosphorylation levels were evaluated in ONHA-derived lysates by immunoblotting.
RESULTS
The coculture of WT RGCs with WT or S1R KO ONHAs increased the total and maximal neurite length. Neurite root and extremity counts increased at 4 and 7 days when WT RGCs were cocultured with WT or S1R KO ONHAs. At all timepoints, the total and maximal neurite length decreased for WT RGCs in coculture with S1R KO ONHAs compared with WT ONHAs. Root and extremity counts decreased for WT RGCs in coculture with S1R KO ONHAs compared with WT ONHAs at 2 and 7, but not 4 days. RGC apoptosis increased in S1R KO ONHA coculture and S1R KO-conditioned medium, compared with WT ONHA coculture or WT-conditioned medium. S1R KO ONHA-derived lysates showed decreased phosphorylated signal transducer and activator of transcription 3 levels compared with WT ONHA-derived lysates.
CONCLUSIONS
The absence of S1R within ONHAs has a deleterious effect on RGC neurite growth and RGC survival, reflected in analysis of WT RGC + S1R KO ONHA indirect cocultures. The data suggest that S1R may enhance ganglion cell survival via glia-mediated mechanisms.
目的
西格玛 1 受体（S1R）在视网膜神经节细胞（RGC）和星形胶质细胞中表达，其激活具有神经保护作用。我们评估了视神经头星形胶质细胞（ONHA）内 S1R 对体外 RGC 生长和存活的贡献。
方法
将野生型（WT）RGC 和 WT 或 S1R 敲除（S1R KO）ONHA 共培养 2、4 或 7 天。测量总神经突长度和最大神经突长度、神经突根和末梢计数。用 TUNEL 测定法测量细胞死亡。通过免疫印迹法评估 ONHA 衍生裂解物中信号转导和转录激活因子 3 的磷酸化水平。
结果
WT RGC 与 WT 或 S1R KO ONHA 共培养可增加总神经突长度和最大神经突长度。当 WT RGC 与 WT 或 S1R KO ONHA 共培养时，4 天和 7 天神经突根和末梢计数增加。在所有时间点，与 WT ONHA 相比，WT RGC 与 S1R KO ONHA 共培养时的总神经突长度和最大神经突长度降低。与 WT ONHA 相比，WT RGC 与 S1R KO ONHA 共培养时，2 天和 7 天而非 4 天神经突根和末梢计数减少。与 WT ONHA 共培养或 WT 条件培养基相比，S1R KO ONHA 共培养和 S1R KO 条件培养基中 RGC 凋亡增加。与 WT ONHA 衍生裂解物相比，S1R KO ONHA 衍生裂解物中磷酸化信号转导和转录激活因子 3 水平降低。
结论
ONHA 内缺乏 S1R 对 RGC 神经突生长和 RGC 存活有有害影响，这反映在 WT RGC+S1R KO ONHA 间接共培养的分析中。数据表明，S1R 可能通过神经胶质细胞介导的机制增强节细胞存活。
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