TY - JOUR
T1 - Emerging model systems and treatment approaches for Leber's hereditary optic neuropathy
T2 - Challenges and opportunities
AU - Bahr, Tyler
AU - Welburn, Kyle
AU - Donnelly, Jonathan
AU - Bai, Yidong
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease mainly affecting retinal ganglion cells (RGCs). The pathogenesis of LHON remains ill-characterized due to a historic lack of effective disease models. Promising models have recently begun to emerge; however, less effective models remain popular. Many such models represent LHON using non-neuronal cells or assume that mutant mtDNA alone is sufficient to model the disease. This is problematic because context-specific factors play a significant role in LHON pathogenesis, as the mtDNA mutation itself is necessary but not sufficient to cause LHON. Effective models of LHON should be capable of demonstrating processes that distinguish healthy carrier cells from diseased cells. In light of these considerations, we review the pathophysiology of LHON as it relates to old, new and future models. We further discuss treatments for LHON and unanswered questions that might be explored using these new model systems.
AB - Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease mainly affecting retinal ganglion cells (RGCs). The pathogenesis of LHON remains ill-characterized due to a historic lack of effective disease models. Promising models have recently begun to emerge; however, less effective models remain popular. Many such models represent LHON using non-neuronal cells or assume that mutant mtDNA alone is sufficient to model the disease. This is problematic because context-specific factors play a significant role in LHON pathogenesis, as the mtDNA mutation itself is necessary but not sufficient to cause LHON. Effective models of LHON should be capable of demonstrating processes that distinguish healthy carrier cells from diseased cells. In light of these considerations, we review the pathophysiology of LHON as it relates to old, new and future models. We further discuss treatments for LHON and unanswered questions that might be explored using these new model systems.
KW - Induced pluripotent stem cells
KW - Leber's hereditary optic neuropathy
KW - Mitochondrial disease
KW - Retinal ganglion cells
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U2 - 10.1016/j.bbadis.2020.165743
DO - 10.1016/j.bbadis.2020.165743
M3 - Review article
C2 - 32105823
AN - SCOPUS:85080994449
SN - 0925-4439
VL - 1866
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 6
M1 - 165743
ER -