Doheny Eye Institute and Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Mitochondrion. 2013 Nov;13(6):841-5. doi: 10.1016/j.mito.2013.05.013. Epub 2013 Jun 6.
Mitochondrial dysfunction in Wolfram Syndrome (WS) is controversial and optic neuropathy, a cardinal clinical manifestation, is poorly characterized. We here describe the histopathological features in postmortem retinas and optic nerves (ONs) from one patient with WS, testing the hypothesis that mitochondrial dysfunction underlies the pathology. Eyes and retrobulbar ONs were obtained at autopsy from a WS patient, and compared with those of a Leber hereditary optic neuropathy (LHON) patient and one healthy control. Retinas were stained with hematoxylin & eosin for general morphology and ONs were immunostained for myelin basic protein (MBP). Immunostained ONs were examined in four "quadrants": superior, inferior, nasal, and temporal. The WS retinas displayed a severe loss of retinal ganglion cells in the macular region similar to the LHON retina, but not in the control. The WS ONs, immunostained for MBP, revealed a zone of degeneration in the temporal and inferior quadrants. This pattern was similar to that seen in the LHON ONs but not in the control. Thus, the WS patient displayed a distinct pattern of optic atrophy observed bilaterally in the temporal and inferior quadrants of the ONs. This arrangement of axonal degeneration, involving primarily the papillomacular bundle, closely resembled LHON and other mitochondrial optic neuropathies, supporting that mitochondrial dysfunction underlies its pathogenesis.
Wolfram 综合征（WS）的线粒体功能障碍存在争议，而视神经病变作为其主要临床表现，其特征描述尚不清楚。我们在此描述了一位 WS 患者死后视网膜和视神经（ON）的组织病理学特征，旨在验证线粒体功能障碍是其病理学基础这一假说。该 WS 患者的眼球和眶内视神经在尸检时被采集，并与一位 Leber 遗传性视神经病变（LHON）患者和一位健康对照者的眼部组织进行了对比。视网膜经苏木精-伊红染色后进行一般形态学检查，视神经行髓鞘碱性蛋白（MBP）免疫染色。对免疫染色的视神经进行了四个象限（上、下、鼻、颞）的检查。WS 患者的视网膜黄斑区出现了严重的神经节细胞丢失，与 LHON 视网膜相似，但在对照组中没有发现。WS 的 MBP 免疫染色视神经显示，颞侧和下侧象限存在一个变性区。这种模式与 LHON 视神经相似，但与对照组不同。因此，WS 患者的视神经呈现出一种双侧颞侧和下侧象限的明显的视神经萎缩模式。这种轴突变性的排列方式，主要累及视盘黄斑束，与 LHON 和其他线粒体视神经病变非常相似，支持线粒体功能障碍是其发病机制的基础。
