The pathological mechanisms and novel therapeutics for Leber's hereditary optic neuropathy
Journal
Journal of the Chinese Medical Association : JCMA
Journal Volume
86
Journal Issue
6
Date Issued
2023-06-01
Author(s)
Yang, Yi-Ping
Foustine, Shania
Hsiao, Yu-Jer
Tsai, En-Tung
Tsai, Fu-Ting
Wang, Chia-Lin
Ko, Yu-Ling
Tai, Hsiao-Yun
Tsai, Yi-Ching
Fu, Yun-Ju
Wang, An-Guor
Chien, Yueh
Abstract
Optic neuropathies were estimated to affect 115 in 100,000 population in 2018. Leber's Hereditary Optic Neuropathy (LHON) as one of such optic neuropathy diseases that was first identified in 1871 and can be defined as a hereditary mitochondrial disease. LHON is associated with three mtDNA point mutations which are G11778A, T14484, and G3460A that affect the NADH dehydrogenase subunits of 4, 6, and 1, respectively. However, in most cases, only one point mutation is involved. Generally, in manifestation of the disease, there are no symptoms until the terminal dysfunction in the optic nerve is observed. Due to the mutations, nicotinamide adenine dinucleotide (NADH) dehydrogenase or complex I is absent and thus ATP production is stopped. This further causes the generation of reactive oxygen species and retina ganglion cells apoptosis. Aside from the mutations, there are several environmental factors such as smoking and alcohol consumption that can be pointed out as the risk factors of LHON. Nowadays, gene therapy has been intensively studied for LHON treatment. Disease models using human induced pluripotent stem cells (hiPSCs) have been utilized for LHON research.
Subjects
Induced pluripotent stem cells | Leber's Hereditary Optic Neuropathy (LHON) | Optic neuropathy | Retina ganglion cell
SDGs
Type
journal article