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Yuji Takihara, Masaru Inatani, Toshihiro Inoue, Keiichiro Iwao, Yoshihiro Takamura, Hidenobu Tanihara; Totally organized mitochondrial axonal transport patterns in retinal ganglion cells of old mice in vivo. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3661.
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© ARVO (1962-2015); The Authors (2016-present)
Histological studies in glaucoma models have suggested disturbances in mitochondrial axonal transport of retinal ganglion cells (RGCs). Similar to other neurodegenerative diseases of the central nervous system, the incidence of glaucoma increases with age. However, whether mitochondrial axonal transport is preserved in aged mammals remains unknown. The purpose of the present study is to examine whether mitochondrial axonal transport patterns that are consistently observed in RGCs of young (2 months), adult (4 months), middle-aged (12-13 months) mice are preserved in RGCs of old mice (23-25 months) in vivo.
Under general anesthesia, intravital imaging (direct in vivo imaging of living animals) of mouse RGCs was performed. We compared mitochondrial axonal transport patterns in young, adult, middle-aged, and old mice.
Intravital imaging of RGCs showed highly dynamic mitochondrial axonal transport in mice aged up to 23-25 months in vivo. We found four mitochondrial axonal transport patterns in vivo: bilateral transport (Bi), continuous transport (Co), transport that pauses in regions where other mitochondria exist (Pe), and transport that pauses in mitochondria-free regions (Pf). Intravital imaging of RGCs showed similar proportions of the four transport patterns (Pe, Co, Pf, and Bi) among the four age groups, indicating that almost all mitochondria were unidirectionally transported in vivo (young, 97.3%; adult, 95.1%; middle-aged, 97.2%; old, 96.8%). The ratios of anterograde to retrograde transport were consistent (approximately 3/2) through the four age groups. In the two transport patterns with pauses (Pe and Pf), the transport velocity of Pf was consistently slower than that of Pe among the four age groups. The almost entirely unidirectional transport of mitochondria and consistent ratios of anterograde/retrograde transport suggest total organization of mitochondrial axonal transport preserved in mice aged up to 23-25 months.
Intravital imaging of mouse RGCs shows that mitochondrial axonal transport is highly dynamic in mice aged up to 23-25 months in vivo. Furthermore, the totally organized mitochondrial axonal transport patterns are preserved in old mice. Our results regarding total organization of mitochondrial axonal transport suggest that even in RGCs of old mice, energy demand by homeostasis does not exceed capacity to resist stresses.
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