Division of Human Genetics and Child Development, Department of Pediatrics, The Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Curr Opin Ophthalmol. 2011 Sep;22(5):325-31. doi: 10.1097/ICU.0b013e328349419d.
Mitochondrial disease is a heterogeneous group of energy metabolism disorders that present across all ages with a wide range of ocular or multisystemic manifestations. This review focuses on recent progress made toward understanding the various ophthalmologic manifestations of primary mitochondrial diseases and discusses the implications of mitochondrial dysfunction, placing particular emphasis on recent investigations into the pathogenesis and emerging therapies for mitochondrial-based ophthalmologic disorders.
Novel pathogenic mitochondrial DNA mutations continue to be detected in diverse ethnic populations for primary mitochondrial ophthalmologic disorders that commonly affect the optic nerve, retina, and extraocular muscles. Promising antioxidant and gene therapy approaches are being actively investigated to treat these ophthalmologic manifestations, as in Leber's hereditary optic neuropathy. Mitochondrial dysfunction is also increasingly implicated in common ophthalmologic disorders of aging, including diabetic retinopathy, age-related macular degeneration, and glaucoma. Several proteins recently recognized to play a role in the mitochondrial oxidative stress response within retinal cells, such as prohibitin and MMP2, may serve as novel biomarkers and therapeutic targets for common ophthalmologic disorders. Therapies that inhibit mitochondrial function and induce apoptosis within tumor cells, such as EDL-155 and curcumin, may offer novel therapeutic agents for ocular neoplasms such as retinoblastoma and uveal melanoma.
Primary mitochondrial genetic disease manifestations can involve almost all aspects of the eye. Mitochondrial dysfunction is increasingly recognized as playing a causative role in the common ophthalmologic disorders in aging. This understanding has unleashed a range of emerging therapeutic approaches for mitochondrial-based ophthalmologic disorders directed at optimizing mitochondrial function.
线粒体疾病是一组异质性的能量代谢障碍，可发生于各个年龄段，具有广泛的眼部或多系统表现。本文重点介绍了原发性线粒体疾病各种眼部表现的最新研究进展，并讨论了线粒体功能障碍的影响，特别强调了最近对基于线粒体的眼科疾病发病机制和新兴治疗方法的研究。
在原发性线粒体眼科疾病中，不断在不同种族人群中检测到新的致病性线粒体 DNA 突变，这些疾病通常影响视神经、视网膜和眼外肌。正在积极研究有前途的抗氧化和基因治疗方法来治疗这些眼部表现，例如莱伯遗传性视神经病变。线粒体功能障碍也越来越多地与衰老相关的常见眼科疾病有关，包括糖尿病性视网膜病变、年龄相关性黄斑变性和青光眼。最近发现几种在视网膜细胞中线粒体氧化应激反应中起作用的蛋白质，如 prohibitin 和 MMP2，可能作为常见眼科疾病的新型生物标志物和治疗靶点。抑制线粒体功能并在肿瘤细胞中诱导细胞凋亡的治疗方法，如 EDL-155 和姜黄素，可能为视网膜母细胞瘤和葡萄膜黑色素瘤等眼部肿瘤提供新的治疗药物。
原发性线粒体遗传疾病的表现几乎可以涉及眼睛的各个方面。线粒体功能障碍越来越被认为是导致衰老相关常见眼科疾病的原因。这种认识引发了一系列针对基于线粒体的眼科疾病的新兴治疗方法，旨在优化线粒体功能。
