Isashiki Y, Nakagawa M, Ohba N, Kamimura K, Sakoda Y, Higuchi I, Izumo S, Osame M
Department of Ophthalmology, Center for Chronic Viral Disease, Kagoshima University Faculty of Medicine, Japan.
Acta Ophthalmol Scand. 1998 Feb;76(1):6-13. doi: 10.1034/j.1600-0420.1998.760103.x.
To scrutinize retinal involvement associated with distinct mitochondrial DNA (mtDNA) defects, we reviewed the records of a consecutive series of patients with various mitochondrial diseases.
Clinical, laboratory and mtDNA studies were performed in: five patients with Kearns-Sayre syndrome (KSS); six patients with chronic progressive external ophthalmoplegia (CPEO); three patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS); three patients with myoclonic epilepsy and ragged-red fibers (MERRF); 20 patients with Leber's hereditary optic neuropathy (LHON); 30 patients with simple diabetes mellitus.
All KSS patients with neurologic and cardiac symptoms associated with a deletion of mtDNA in muscle biopsy specimens showed widespread retinal pigmentary changes characterized by salt- and pepper-like appearance of the fundus. Three of six patients with CPEO, a mild variant of KSS, showed subtle defects at the level of retinal pigment epithelium of the posterior pole, although mtDNA deletion was similar to that in KSS. Of three patients with MELAS syndrome, one patient showed juvenile cataract and mild retinal pigmentary defect in the posterior pole. Of three patients with MERRF syndrome associated with a mtDNA mutation at nucleotide position (np) 8344, one patient showed mild pigment disorder in the posterior pole in addition to optic neuropathy. Two of 20 patients with LHON associated with a mtDNA mutation at np 11778 showed mild pigmentary defect in the macula together with typical optic neuropathy. In addition, two of 30 patients with isolated diabetes mellitus showed a mtDNA mutation at np 3243 (MELAS mutation), but they did not present with any other neurologic or multisystem disorder.
The retina, in particular the retinal pigment epithelium, is highly vulnerable to be involved by mtDNA defect, and the retinopathy is phenotypically variable and frequently subclinical, depending to some extent on the type or site of mtDNA defect.
为了仔细研究与不同线粒体DNA（mtDNA）缺陷相关的视网膜病变，我们回顾了一系列连续的患有各种线粒体疾病患者的病历。
对以下患者进行了临床、实验室和mtDNA研究：5例患有卡恩斯-塞尔综合征（KSS）的患者；6例患有慢性进行性外眼肌麻痹（CPEO）的患者；3例患有线粒体肌病、脑病、乳酸性酸中毒和卒中样发作（MELAS）的患者；3例患有肌阵挛性癫痫伴破碎红纤维（MERRF）的患者；20例患有Leber遗传性视神经病变（LHON）的患者；30例患有单纯糖尿病的患者。
所有在肌肉活检标本中存在mtDNA缺失且伴有神经和心脏症状的KSS患者均表现出广泛的视网膜色素沉着改变，其特征为眼底呈椒盐样外观。6例CPEO患者（KSS的一种轻度变异型）中有3例在后极部视网膜色素上皮水平存在细微缺陷，尽管其mtDNA缺失情况与KSS患者相似。3例MELAS综合征患者中，1例出现青少年白内障和后极部轻度视网膜色素沉着缺陷。3例与mtDNA核苷酸位置（np）8344突变相关的MERRF综合征患者中，1例除视神经病变外，后极部还存在轻度色素紊乱。20例与np 11778处mtDNA突变相关的LHON患者中有2例除典型视神经病变外，黄斑区还存在轻度色素沉着缺陷。此外，30例单纯糖尿病患者中有2例在np 3243处存在mtDNA突变（MELAS突变），但他们未出现任何其他神经或多系统疾病。
视网膜，尤其是视网膜色素上皮，极易受到mtDNA缺陷的影响，视网膜病变在表型上具有多样性且常为亚临床状态，在一定程度上取决于mtDNA缺陷的类型或部位。
