Histopathology and Functional Correlations in a Patient with a Mutation in RPE65, the Gene for Retinol Isomerase
Histopathology and Functional Correlations in a Patient with a Mutation in RPE65, the Gene for Retinol Isomerase
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DOI：
10.1167/iovs.11-7973
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发表时间：
2011-10-01
影响因子：
4.4
通讯作者：
Hollyfield, Joe G.
中科院分区：
文献类型：
--
作者：
Bonilha, Vera L.;Rayborn, Mary E.;Hollyfield, Joe G.
目的。本文作者描述了一名56岁患者死后供体眼视网膜和视网膜色素上皮（RPE）的结构特征，该患者患有纯合子错义RPE65突变（Ala132Thr），并将该病理与患者51岁时最后一次测量的视觉功能联系起来。眼睛在死后13.5小时内被摘除。对黄斑和周围的代表性区域进行光镜和电镜处理。利用免疫荧光技术定位RPE65、视紫红质和视锥蛋白的分布。将RPE的自体荧光与两眼年龄相近的正常供体进行比较。组织学检查显示视网膜大部分区域的视杆细胞和视锥细胞丢失，视网膜血管减弱，双眼RPE变薄。黄斑中存在少量高度无序的视锥细胞，同时显示出视锥细胞阻滞蛋白和红/绿或蓝视蛋白的标记。与对照组相比，RPE65免疫反应性和RPE自身荧光在所有研究区域均降低。远周视杆可见视紫红质标记。视神经轴突数量减少。死亡前5年的视力下降、视野狭窄和视网膜电图（ERGs）减少的临床表现与黄斑中存在的视锥细胞数量少和周围光感受器的广泛丧失有关。RPE中自身荧光的缺失表明视网膜上的光感受器细胞可能缺失了很长一段时间。讨论了可能导致光感受器细胞死亡的机制。（Invest Ophthalmol Vis Sci. 2011;52:8381-8392） DOI: 10.1167/iovs.117973
PURPOSE. Here the authors describe the structural features of the retina and retinal pigment epithelium (RPE) in postmortem donor eyes of a 56-year-old patient with a homozygous missense RPE65 mutation (Ala132Thr) and correlate the pathology with the patient's visual function last measured at age 51.METHODS. Eyes were enucleated within 13.5 hours after death. Representative areas from the macula and periphery were processed for light and electron microscopy. Immunofluorescence was used to localize the distribution of RPE65, rhodopsin, and cone arrestin. The autofluorescence in the RPE was compared with that of two normal eyes from age-similar donors.RESULTS. Histologic examination revealed the loss of rods and cones across most areas of the retina, attenuated retinal vessels, and RPE thinning in both eyes. A small number of highly disorganized cones were present in the macula that showed simultaneous labeling with cone arrestin and red/green or blue opsin. RPE65 immunoreactivity and RPE autofluorescence were reduced compared with control eyes in all areas studied. Rhodopsin labeling was observed in rods in the far periphery. The optic nerve showed a reduced number of axons.CONCLUSIONS. The clinical findings of reduced visual acuity, constricted fields, and reduced electroretinograms (ERGs) 5 years before death correlated with the small number of cones present in the macula and the extensive loss of photoreceptors in the periphery. The absence of autofluorescence in the RPE suggests that photoreceptor cells were probably missing across the retina for extended periods of time. Possible mechanisms that could lead to photoreceptor cell death are discussed. (Invest Ophthalmol Vis Sci. 2011;52:8381-8392) DOI: 10.1167/iovs.117973