Developmental expression profile of the optic atrophy gene product: OPA1 is not localized exclusively in the mammalian retinal ganglion cell layer
Developmental expression profile of the optic atrophy gene product: OPA1 is not localized exclusively in the mammalian retinal ganglion cell layer
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DOI：
10.1167/iovs.03-1093
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发表时间：
2004-06-01
影响因子：
4.4
通讯作者：
Votruba, M
中科院分区：
文献类型：
--
作者：
Aijaz, S;Erskine, L;Votruba, M
目的。常染色体显性遗传性视神经萎缩以视网膜神经节细胞的原发变性和视神经萎缩为特征。OPA1基因编码一个960个氨基酸的蛋白质。在目前的研究中，研究了OPA1在发育中和成年小鼠眼组织以及成人人眼中的时间和空间定位。由于BST/+小鼠一直被认为是ADOA的模型，因此我们还检测了mOPA1在BST/+视网膜中的表达。方法：用一种针对OPA1 C端肽的多克隆抗体，用免疫组织化学方法检测mOPA1在野生型胚胎和出生后小鼠眼组织以及BST/+视网膜中的表达。结果：mOPA1在视网膜和视神经中的表达始于胚胎15天，与随后发育的神经节细胞层(GCL)相对应，在出生后0天至P1天达到高峰。MOPA1的表达在P2后急剧下降，但至少在视网膜的GCL、内丛状层(IPL)和内核层(INL)以及视神经中表达在基础水平，直到P12。在成年BST/+视网膜中，mOPA1在GCL和IPL中强表达，在INL中弱表达。在成人人眼中，OPA1表达于视网膜的GCL、IPL、INL和外丛状层(OPL)，仅见于有髓区域。结论OPA1不局限于哺乳动物视网膜的GCL，它的表达延伸到IPL、INL和OPL。OPA1在人视神经中表达于筛板以外的有髓区域，而在小鼠视神经中的表达较弱。在BST/+小鼠视网膜中，尽管存在结构缺陷，mOPA1的表达与野生型成年小鼠视网膜中观察到的类似。这些观察结果表明，OPA1的作用比之前预期的更广泛。
PURPOSE. Autosomal dominant optic atrophy (ADOA) is characterized by primary degeneration of retinal ganglion cells and atrophy of the optic nerve. The OPA1 gene encodes a 960-amino-acid protein. in the current study the temporal and spatial localization of OPA1 were examined in developing and adult murine ocular tissues and the adult human eye. Because the Bst/+ mouse has been postulated as a model of ADOA, the mOPA1 expression in the Bst/+ retina was also examined.METHODS. A polyclonal antibody generated against a C-terminal peptide of OPA1 was used to assess by immunohistochemistry the expression of mOPA1 in the wild-type embryonic and postnatal mouse ocular tissues and the Bst/+ retina. Western blot analyses of total proteins from a panel of adult human tissues were used to examine the expression of human OPA1, and spatial localization was assessed by immunohistochemistry.RESULTS. The ocular expression of mOPA1 begins at E15 in the inner retina in a location corresponding to that of the subsequently developing ganglion cell layer (GCL) and peaks between postnatal day (P)0 and P1 in the retina and the optic nerve. There is a sharp decline in mOPA1 expression after P2, but it is expressed at a basal level until at least P 12 in the GCL, inner plexiform layer (IPL), and inner nuclear layer (INL) of the retina as well as in the optic nerve. In the adult Bst/+ retina, mOPA1 is strongly expressed in the GCL and IPL and weakly in the INL. In the adult human eye, OPA1 is expressed in the GCL, IPL, INL, and outer plexiform layer (OPL) of the retina and in the optic nerve, where it is observed only in the myelinated region.CONCLUSIONS. OPA1 is not restricted to the GCL of the mammalian retina, and its expression extends into the IPL, INL, and OPL. OPA1 is distinctly expressed in the myelinated region beyond the lamina cribrosa in the human optic nerve, whereas its expression is weaker in the mouse optic: nerve. In the Bst/+ mouse retina, despite the structural defects, mOPA1 expression is comparable to that observed in the wild-type adult mouse retina. These observations suggest a wider role for OPA1 than previously anticipated.