Li Z Y, Jacobson S G, Milam A H
University of Washington School of Medicine, Department of Ophthalmology, Seattle 98195.
Exp Eye Res. 1994 Apr;58(4):397-408. doi: 10.1006/exer.1994.1032.
The retinas from a 68-year-old man with autosomal dominant retinitis pigmentosa caused by the threonine-17-methionine rhodopsin mutation were studied. Patients with this mutation have a characteristic clinical phenotype that shows intra- and interfamilial consistency. The retinas were examined by light and electron microscopy, including immunocytochemistry with markers for rods, cones, the retinal pigment epithelium, the interphotoreceptor matrix and Müller cells, and the results were correlated with those from visual function tests performed fourteen months before death. Grossly, both retinas had heavy deposits of bone spicule-like pigmentation inferiorly, but the superior retinas showed much less pigmentation. The maculas contained no rods and an incomplete monolayer of cone somata, consistent with the patient's severely reduced central vision. The inferior retinas contained no rods and rare cone somata, correlating with an absolute scotoma in the superior field. The superior retinas had near-normal-appearing rods and cones in the far periphery and a gradient from the midperipheral to central retina of progressively shortened outer segments and loss of photoreceptors, consistent with the patient's reduced rod and cone electroretinograms and retained rod and cone sensitivities in the inferior peripheral field by perimetry. Immunocytochemistry with rod-specific markers was qualitatively normal in the superior mid to far peripheral retina. Electron microscopic immunogold labeling with anti-rhodopsin revealed similar densities of gold particles over rod outer segments of the RP and a normal donor retina. Degenerate photoreceptors in the superior equatorial region of the RP retina had short outer segments, and some rods had surface labeling with anti-rhodopsin of the inner segments, somata and synapses. The results indicate regional retinal differences of disease severity in this genotype and that rods in the superior peripheral retina have normal morphology despite the presence of the mutant allele. To the authors' knowledge, this is the first detailed study of rod photoreceptors in the retina of an RP patient with a rhodopsin mutation.
对一名68岁男性的视网膜进行了研究，该男性患有由苏氨酸-17-甲硫氨酸视紫红质突变引起的常染色体显性遗传性视网膜色素变性。具有这种突变的患者具有特征性的临床表型，在家族内和家族间具有一致性。通过光镜和电镜对视网膜进行检查，包括使用针对视杆细胞、视锥细胞、视网膜色素上皮、光感受器间基质和米勒细胞的标志物进行免疫细胞化学检测，并将结果与患者死亡前14个月进行的视觉功能测试结果相关联。大体上，两个视网膜下方都有大量骨针状色素沉着，但上方视网膜色素沉着较少。黄斑区没有视杆细胞，视锥细胞胞体单层不完整，这与患者严重降低的中心视力一致。下方视网膜没有视杆细胞，视锥细胞胞体罕见，这与上方视野的绝对暗点相关。上方视网膜在最外周的视杆细胞和视锥细胞外观接近正常，从中外周到中央视网膜存在渐变，即外节逐渐缩短，光感受器丧失，这与患者视杆细胞和视锥细胞视网膜电图降低以及通过视野检查在下方外周视野保留视杆细胞和视锥细胞敏感性一致。使用视杆细胞特异性标志物进行的免疫细胞化学检测在上方中至外周视网膜中定性正常。用抗视紫红质进行的电子显微镜免疫金标记显示，视网膜色素变性患者和正常供体视网膜的视杆细胞外节上的金颗粒密度相似。视网膜色素变性视网膜赤道上方区域退化的光感受器外节较短，一些视杆细胞的内节、胞体和突触有抗视紫红质的表面标记。结果表明该基因型中视网膜疾病严重程度存在区域差异，并且尽管存在突变等位基因，上方外周视网膜中的视杆细胞形态正常。据作者所知，这是对患有视紫红质突变的视网膜色素变性患者视网膜中视杆光感受器的首次详细研究。
