Lack of fundus autofluorescence to 488 nanometers from childhood on in patients with early-onset severe retinal dystrophy associated with mutations in RPE65
Lack of fundus autofluorescence to 488 nanometers from childhood on in patients with early-onset severe retinal dystrophy associated with mutations in RPE65
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DOI：
10.1016/j.ophtha.2004.01.033
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发表时间：
2004-08-01
期刊：
影响因子：
13.7
通讯作者：
Preising, MN
中科院分区：
文献类型：
--
作者：
Lorenz, B;Wabbels, B;Preising, MN
目的：眼底自发荧光是由于视网膜色素上皮细胞（RPE）中脂褐素的积累，这是由脱落的感光细胞外节盘的N-亚视黄基-磷脂酰-乙醇胺的不完全消化引起的。自发荧光的改变反映了RPE的脂褐素含量的变化。由于RPE中全反式视黄醇异构化的缺陷，RPE 65的两个等位基因上的突变导致视紫红质的形成不存在或大大减少。因此可以改变自体荧光。本研究旨在评估与RPE 65两个等位基因突变相关的早发性严重视网膜营养不良（EOSRD，或早发性视杆-视锥营养不良）患者的眼底自发荧光。设计：病例系列。参与者和对照：10名10- 55岁EOSRD和RPE 65复合杂合或纯合突变患者。为了进行比较，对6名杂合子父母和2名患有其他形式EOSRD的患者进行了检查。方法：除了标准的临床和电生理检查外，参与者还使用共聚焦扫描激光检眼镜进行自发荧光成像。其中三名患者还接受了光学相干断层扫描（OCT）检查，以评估视网膜变性的状态。此前已报道了7例患者的突变;其他患者通过聚合酶链反应-单链构象多态性和直接测序来研究RPE 65和卵磷脂视黄醇酰基转移酶（LRAT）的突变。主要结果测量：眼底自发荧光和OCT。结果：所有具有复合杂合或纯合RPE 65突变的患者均未发现或发现极少量自发荧光。杂合子父母的自体荧光正常。2例EOSRD患儿存在自体荧光，与RPE 65或LRAT（另一个参与视黄醇再循环的基因）突变无关。在年轻患者的光学相干断层扫描显示，他们的健康，杂合子parents.Conclusions：缺乏自发荧光与RPE 65突变相关的EOSRD患者的视网膜内外观相似，是按照生化缺陷，可作为这种基因型的临床标志物。年轻患者的光学相干断层扫描结果表明，尽管没有自体荧光，但仍有活性的光感受器。(C)2004年，美国眼科学会。
Purpose: Fundus autofluorescence is due to accumulation of lipofuscin in the retinal pigment epithelium (RPE) resulting from incomplete digestion of N-retinylidene-phosphatidyl-ethanolamine from shed photoreceptor outer segment discs. Alteration in autofluorescence reflects changes in lipofuscin content of the RPE. Mutations on both alleles of RPE65 result in absent or largely decreased formation of rhodopsin, due to a defect in all-trans retinol isomerization in the RPE. Autofluorescence could therefore be altered. This study was conducted to evaluate fundus autofluorescence in patients with early-onset severe retinal dystrophy (EOSRD, or early-onset rod-cone dystrophy) associated with mutations on both alleles of RPE65.Design: Case series.Participants and Controls: Ten 10- to 55-year-old patients with EOSRD and compound heterozygous or homozygous mutations in RPE65. For comparison, 6 heterozygous parents and 2 patients with other forms of EOSRD were examined.Methods: Participants underwent, in addition to standard clinical and electrophysiological examination, autofluorescence imaging using a confocal scanning laser ophthalmoscope. Three of the patients were also examined by optical coherence tomography (OCT) to evaluate the status of retinal degeneration. Mutations in 7 patients have been reported previously; the other patients were investigated by polymerase chain reaction-single-strand conformation polymorphism and direct sequencing for mutations in RPE65 and lecithin retinol acyltransferase (LRAT).Main Outcome Measures: Fundus autofluorescence and OCT.Results: Absent or minimal autofluorescence was found in all patients with compound heterozygous or homozygous RPE65 mutations. Autofluorescence was normal in the heterozygous parents. Autofluorescence was present in 2 children with EOSRD not associated with mutations in RPE65 or LRAT, another gene involved in retinol recycling. Optical coherence tomography in younger patients revealed an intraretinal appearance similar to that of their healthy, heterozygous parents.Conclusions: Lack of autofluorescence in patients with EOSRD associated with mutations in RPE65 is in accordance with the biochemical defect and can be used as a clinical marker of this genotype. Optical coherence tomography results in younger patients would indicate still viable photoreceptors despite the absence of autofluorescence. (C) 2004 by the American Academy of Ophthalmology.