Crumbs homolog 1 (CRB1) mutations result in a thick human retina with abnormal lamination
Crumbs homolog 1 (CRB1) mutations result in a thick human retina with abnormal lamination
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DOI：
10.1093/hmg/ddg117
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发表时间：
2003-05-01
影响因子：
3.5
通讯作者：
Stone, EM
中科院分区：
文献类型：
--
作者：
Jacobson, SG;Cideciyan, AV;Stone, EM
CRB1是果蝇Crumbs的人类同源物，CRB1的突变导致视网膜的常染色体隐性致盲疾病。尽管Crumbs与顶部-基底上皮极性和感光细胞形态发生有关，但CRB1在正常或患病视网膜中的作用仍不清楚。我们表征了CRB1突变患者体内的视网膜组织，发现与迄今为止研究的其他遗传性视网膜变性不同，CRB1突变视网膜的横截面非常厚，缺乏正常成人视网膜的不同层。在视神经周围有粗糙的外区和内区以及厚的表层。CRB1突变的异常视网膜结构类似于未成熟的正常视网膜。结果表明，CRB1疾病通路通过中断自然发生的细胞凋亡来干扰正常人类视网膜组织的发育。
Mutations in CRB1, the human homolog of Drosophila Crumbs, cause autosomal recessive blinding disorders of the retina. Whereas Crumbs is implicated in apical-basal epithelial polarity and photoreceptor morphogenesis, the role of CRB1 in normal or diseased retina remains unclear. We characterized the retinal organization in vivo of patients with CRB1 mutations and found that, unlike other inherited retinal degenerations studied to date, the CRB1 mutant retinas are remarkably thick in cross-section and lack the distinct layers of normal adult retina. There are coarse outer and inner zones and a thick surface layer around the optic nerve. The abnormal retinal architecture in CRB1 mutations resembles that of immature normal retina. The results suggest that the CRB1 disease pathway disturbs the development of normal human retinal organization by interrupting naturally occurring apoptosis.