Acid-Sensing Ion Channel 3 in Retinal Function and Survival
Acid-Sensing Ion Channel 3 in Retinal Function and Survival
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DOI：
10.1167/iovs.08-3028
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发表时间：
2009-05-01
影响因子：
4.4
通讯作者：
Lingueglia, Eric
中科院分区：
文献类型：
--
作者：
Ettaiche, Mohammed;Deval, Emmanuel;Lingueglia, Eric
目的.视网膜细胞外pH值的变化直接影响视网膜活性和光传导。作者分析了ASIC 3（细胞外酸中毒传感器）在啮齿动物视网膜中的表达，并使用ASIC 3基因敲除小鼠来探讨其在视网膜功能和存活中的作用。ASIC 3的表达和作用通过免疫定位和通过视网膜电图、视网膜组织学（光学和电子显微镜）、胶质细胞酸性蛋白（GFAP）的表达、细胞凋亡分析（TUNEL测定）和视网膜神经节细胞（RGC）原代培养物中的膜片钳记录比较来自不同年龄的野生型和敲除小鼠的视网膜来检查。ASIC 3存在于光感受器的杆内段和水平无长突细胞中。ASIC 3也在RGC中检测到，但对培养的RGC中记录的ASIC电流没有显著贡献。在2至3个月时，敲除小鼠经历暗视视网膜电图a波振幅的19%增强和b波振幅的伴随增加而没有视网膜结构的改变。年长的（8个月大）基因敲除小鼠的暗视a波和b波分别减少69%和64%，并且与视网膜完全紊乱和杆内节退化相关的振荡电位振幅减少。8月龄和12月龄时进行的GFAP和TUNEL染色显示Muller细胞中GFAP表达上调，并且在内部和外部视网膜中存在凋亡细胞。ASIC 3的失活在2至3个月时增强视觉转导，但诱导迟发性视杆细胞死亡，这表明ASIC 3在维持视网膜完整性方面具有重要作用。（Invest Ophthalmol维斯科学。2009;50：2417-2426）DOI：10.1167/iovs.08-3028
PURPOSE. Changes in extracellular pH occur in the retina and directly affect retinal activity and phototransduction. The authors analyzed the expression in rodent retina of ASIC3, a sensor of extracellular acidosis, and used ASIC3 knockout mice to explore its role in retinal function and survival.METHODS. The expression and the role of ASIC3 were examined by immunolocalization and by comparing retinas from wildtype and knockout mice at different ages through electroretinography, retinal histology (light and electron microscopy), expression of glial fibrillary acidic protein (GFAP), analysis of cell apoptosis (TUNEL assay), and patch-clamp recordings in primary cultures of retinal ganglion cells (RGCs).RESULTS. ASIC3 is present in the rod inner segment of photo-receptors and in horizontal and some amacrine cells. ASIC3 is also detected in RGCs but does not significantly contribute to ASIC currents recorded in cultured RGCs. At 2 to 3 months, knockout mice experience a 19% enhancement of scotopic electroretinogram a-wave amplitude and a concomitant increase of b-wave amplitude without alteration of retinal structure. Older (8-month-old) knockout mice have 69% and 64% reductions in scotopic a-and b-waves, respectively, and reductions in oscillatory potential amplitudes associated with complete disorganization of the retina and degenerating rod inner segments. GFAP and TUNEL staining performed at 8 and 12 months of age revealed an upregulation of GFAP expression in Muller cells and the presence of apoptotic cells in the inner and outer retina.CONCLUSIONS. Inactivation of ASIC3 enhances visual transduction at 2 to 3 months but induces late-onset rod photoreceptor death, suggesting an important role for ASIC3 in maintaining retinal integrity. (Invest Ophthalmol Vis Sci. 2009;50:2417-2426) DOI:10.1167/iovs.08-3028