A retinal neuronal developmental wave of retinoschisin expression begins in ganglion cells during layer formation
A retinal neuronal developmental wave of retinoschisin expression begins in ganglion cells during layer formation
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DOI：
10.1167/iovs.04-0156
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发表时间：
2004-09-01
影响因子：
4.4
通讯作者：
Sieving, PA
中科院分区：
文献类型：
--
作者：
Takada, Y;Fariss, RN;Sieving, PA
目的。视网膜神经节蛋白基因RS-1的突变会导致幼年型X-连锁视网膜劈裂症(XLRS)，这是一种以视网膜内层分层为特征的营养不良，导致视力障碍。虽然视黄醇蛋白(retinoschisin Protein，RS)在视网膜外部的光感受器中大量表达，但XLRS病影响到视网膜最内层，包括含有视网膜神经节细胞(RGCs)的神经纤维层。结合临床疾病的组织病理学和电生理特点，本研究旨在探讨RS-1在视网膜发育过程中的局部细胞表达。方法应用免疫组织化学、共聚焦免疫荧光显微镜、催化报告沉积原位杂交、激光捕获显微切割/RT-PCR.结果：RS-1蛋白和RS-1mRNA在胚胎至成年小鼠视网膜细胞中定位于特定类型的细胞。随着更多的神经元类别的诞生和突触层的形成，表达以空间和时间发展波的形式向视网膜后方移动。在双极细胞与光感受器建立功能性突触的过程中，视网膜电信号b波的出现证明了RS的表达。结论除水平细胞外，所有主要类型的成年视网膜神经元都表达RS蛋白和mRNA，强烈提示视网膜内层的视黄丝蛋白是由局部合成的，而不是先前提出的从视网膜远端光感受器运输的。成熟的视网膜内神经元持续表达RS支持蛋白质替代治疗策略的可能性，以治疗婴儿和成人XLRS。
PURPOSE. Mutations in the retinoschisin gene, RS-1, cause juvenile X-linked retinoschisis (XLRS), a dystrophy characterized by delamination of the inner retinal layers, leading to visual impairment. Although the retinoschisin protein (RS) is expressed most abundantly in photoreceptors in the outer retina, XLRS disease affects the innermost retinal layers, including the nerve fiber layer that contains retinal ganglion cells (RGCs). Considering the histopathological and electrophysiological characteristics of the clinical disease, the present study was conducted to evaluate the local cellular expression of RS-1 during retinal development.METHODS. RS protein and RS-1 mRNA were localized to specific retinal cell types in embryonic to adult mice by immunohistochemistry, confocal immunofluorescence microscopy, catalyzed reporter deposition in situ hybridization, and laser capture microdissection/RT-PCR.RESULTS. RS-1 mRNA was expressed first in RGCs by postnatal day ( P) 1, after terminal differentiation. Expression then moved posteriorly through the retina in a spatial and temporal developmental wave, as additional neuronal classes were born and synaptic layers were formed. RS was expressed by bipolar cells at a time when these neurons were establishing functional synapses with photoreceptors, evidenced by the appearance of the electroretinogram b-wave between P12 and P14.CONCLUSIONS. All major classes of adult retinal neurons, with the possible exception of horizontal cells, express RS protein and mRNA, strongly suggesting that retinoschisin in the inner retina is synthesized locally rather than being transported, as earlier proposed, from distal retinal photoreceptors. Continued expression of RS by mature inner-retinal neurons supports the possibility of a therapeutic strategy of protein replacement to treat both infants and adults with XLRS.