Histopathologic and immunocytochemical analysis of the retina and ocular tissues in Batten disease
Histopathologic and immunocytochemical analysis of the retina and ocular tissues in Batten disease
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巴顿氏病视网膜和眼组织的组织病理学和免疫细胞化学分析
DOI：
10.1016/s0161-6420(00)00264-5
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发表时间：
2000-09-01
期刊：
影响因子：
13.7
通讯作者：
Milam, AH
中科院分区：
文献类型：
--
作者：
Bensaoula, T;Shibuya, H;Milam, AH
目的：描述Batten病视网膜变性的病理生理特征（青少年神经元蜡样质脂褐质沉积症[JNCL]）由CLN 3基因突变引起。将一名22岁JNCL患者的视网膜和其他眼组织与一名30岁健康人的相同组织进行比较，方法：采用组织病理学和免疫荧光技术对10例老年人的视网膜、角膜、结膜和睫状体进行基因分型。基因组DNA进行聚合酶链反应（PCR）和核苷酸序列分析。结果：JNCL供体为杂合子，与大多数JNCL患者一样，其CLN 3基因有1 kb的缺失，另一个等位基因在外显子6有一个碱基对缺失，导致读码框移位。JNCL视网膜的大体病理学与视网膜色素变性相似，包括骨针色素沉积。组织学研究显示所有视网膜层的神经元丢失。免疫荧光标记的抗体视紫红质，恢复，锥视蛋白表现出退化杆和锥短外段在远周边。自发荧光脂色素颗粒在神经节细胞和内核层的一些细胞中很突出，但在光感受器中没有。视网膜色素上皮细胞（RPE）的脂褐素颗粒比对照标本少。在睫状体和结膜的上皮细胞中发现了脂褐素颗粒的数量增加，但在JNCL eye.Conclusions的角膜中没有发现：免疫荧光研究显示，在远周边退化的杆和锥。RPE中脂褐质颗粒减少，与光感受器外节的损失一致。新的发现，退化的光感受器不包含自发荧光夹杂物表明，颗粒积累可能不会先于感光细胞变性JNCL。在退化的视杆细胞和视锥细胞中存在正常的光感受器蛋白表明，如果开发出治疗Batten病的方法，这些细胞可能能够进行功能性再生。眼科学2000;107：1746-1753（C）2000，美国眼科学会。
Purpose: To describe the pathophysiologic features of retinal degeneration in Batten disease (juvenile neuronal ceroid lipofuscinosis [JNCL]) caused by mutations in the CLN3 gene.Study Design: Comparative human tissue study.Materials: The retina and other ocular tissues of a 22-year-old man with JNCL were compared with the same tissues of a healthy 30-year-old man. DNA from whole blood and RNA from retina were used for genotype analysis.Methods: The retinas, corneas, conjunctiva, and ciliary body were processed for histopathologic and immunofluorescence analysis. Genomic DNA was subjected to polymerase chain reaction (PCR) and nucleotide sequence analyses. Reverse transcriptase/PCR and sequence analysis were performed on retinal RNA.Results: The JNCL donor was heterozygous for a similar to 1 kb deletion in CLN3, as found in most JNCL patients, The other allele had a single base pair deletion in exon 6 that resulted in a frame shift. Gross pathology of the JNCL retina resembled that in retinitis pigmentosa, including deposits of bone spicule pigment. Histopathologic studies revealed loss of neurons from all retinal layers. Immunofluorescence labeling with antibodies to rhodopsin, recoverin, and cone opsin demonstrated degenerate rods and cones with short outer segments in the far periphery. Autofluorescent lipopigment granules were prominent in ganglion cells and some cells of the inner nuclear layer, but not in the photoreceptors. The retinal pigment epithelium (RPE) had fewer lipofuscin granules than the control specimen. Increased numbers of lipofuscin granules were found in the epithelia of the ciliary body and conjunctiva, but not in the cornea of the JNCL eye.Conclusions: Immunofluorescence studies revealed degenerate rods and cones in the far periphery. Lipofuscin granules were decreased in the RPE, consistent with loss of photoreceptor outer segments. The novel finding that degenerate photoreceptors did not contain autofluorescent inclusions suggests that granule accumulation may not precede photoreceptor degeneration in JNCL. The presence of normal photoreceptor proteins in the degenerate rods and cones suggests that these cells may be capable of functional regeneration if a therapy for Batten disease is developed. Ophthalmology 2000;107:1746-1753 (C) 2000 by the American Academy of Ophthalmology.