Schroeder B, Hesse L, Brück W, Gal A
Augenklinik der Philipps-Universität, Marburg, Germany.
Ophthalmic Genet. 1997 Jun;18(2):71-7. doi: 10.3109/13816819709057118.
To determine the clinical, histopathological, and immunohistochemical ocular changes associated with a null mutation in the Norrie disease protein (NDP) gene.
Tissue from a six-month-old boy with bilateral retrolental membranes and retinal detachment was obtained during vitreoretinal surgery. Histological sections were stained immunohistochemically with specific antibodies. No eye diseases with severe visual impairment or blindness were reported in the parents and their families. The NDP gene was analyzed by standard molecular genetic methods.
A severe reduction in the number of retinal ganglion cells and a largely disarranged and hypoplastic inner nuclear layer were visible in the tissue specimen. Areas of the tissue with advanced pathology displayed massive fibrovascular proliferation in the vitreous cavity. Shrinkage and traction resulted in folding and detachment of the outer retina. Immunohistochemical reactivity for MIB(1) antigen demonstrated many proliferating cells in the vitreous, but no proliferative activity in the neuroretina. Retinal neurons showed a high grade of differentiation and expressed uniformly neuron-specific enolase and synaptophysin. A 1-base pair insertion (544/545insA) in the NDP gene was found in the affected boy. This mutation predicts a 'functional null-allele' due to a shift in the reading frame and, thus, a premature termination of mRNA translation after 55 instead of 133 amino acids.
Loss of function of the NDP gene causes marked hypoplasia of the inner retinal cell layers and fibrovascular proliferation in the vitreous cavity, leading to retinal folding and detachment. The NDP therefore seems to play a critical role in terminal differentiation of the inner retinal cell layers and establishment and maintaining of anti-proliferative cellular interactions in the vitreous.
确定与诺里病蛋白（NDP）基因无效突变相关的临床、组织病理学和免疫组化眼部变化。
在玻璃体视网膜手术中获取了一名6个月大患有双侧晶状体后膜和视网膜脱离男孩的组织。组织切片用特异性抗体进行免疫组化染色。其父母及其家族中均未报告有严重视力损害或失明的眼部疾病。通过标准分子遗传学方法分析NDP基因。
在组织标本中可见视网膜神经节细胞数量严重减少，内核层明显排列紊乱且发育不全。病变进展区域的组织在玻璃体腔中显示出大量纤维血管增生。萎缩和牵拉导致视网膜外层折叠和脱离。MIB(1)抗原的免疫组化反应显示玻璃体中有许多增殖细胞，但神经视网膜中无增殖活性。视网膜神经元显示出高度分化，并均匀表达神经元特异性烯醇化酶和突触素。在患病男孩中发现NDP基因有一个1个碱基对的插入（544/545insA）。由于阅读框移位，该突变预测为“功能性无效等位基因”，因此mRNA翻译在55个氨基酸后提前终止，而不是133个氨基酸。
NDP基因功能丧失导致视网膜内层细胞层明显发育不全和玻璃体腔纤维血管增生，导致视网膜折叠和脱离。因此，NDP似乎在视网膜内层细胞层的终末分化以及玻璃体中抗增殖细胞相互作用的建立和维持中起关键作用。
