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D. M. Inman, J. M. Knox, R. S. Morrison, P. J. Horner; DBA/2J Mitochondria Morphology and Distribution Varies With Age and Increasing IOP. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2140.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal ganglion cell axons degenerate in glaucoma. In the DBA/2J mouse model of glaucoma, the slowest conducting, smallest caliber axons degenerate concomitant with significant decreases in optic nerve ATP levels. In general, there is a positive relationship between mitochondrial size and potential energy output: larger mitochondria make more ATP. Additionally, position and number of mitochondria can provide insight into metabolic health and energetic capacity. We undertook an analysis of mitochondria in the DBA/2J optic nerve in order to determine whether the age and IOP-dependent ATP deficit is intrinsic to the RGC axon.
Longitudinal electron micrographs of mitochondria in DBA/2J optic nerve at 3, 6, 10 months were compared to age-matched C57Bl/6 optic nerve micrographs. Mitochondria in digitized EM negatives were analyzed using ImageJ.
Mitochondria numbers peak at 6 months of age in the DBA/2J optic nerve, and remain constant through 10 months of age. This contrasts with C57Bl/6 RGC axons, in which a significant decrease in mitochondrial number from 6 to 10 months was observed. Mitochondria size (length and width) varied in RGC axons of DBA/2J but not C57Bl/6. The distance between mitochondria is similar across all ages in the DBA/2J, while the distance between mitochondria at 6 months is significantly greater in DBA/2J than in the C57Bl/6 RGC axons. In DBA/2J axons at 6 months, solitary mitochondria within an axon are more prevalent; however, when multiple mitochondria are observed, they are in close proximity. There are more mitochondria clusters at 10 months in C57Bl/6, though the distance between adjacent mitochondria has increased with age. The proximity of mitochondria to the axon membrane in the DBA/2J RGC axons decreases with age while it increases in C57Bl/6. DBA/2J mitochondria are on the whole further from the axon membrane than C57Bl/6 mitochondria.
Decreases in mitochondria size in DBA/2J RGC axons with age suggest decreased energetic potential. Fewer clusters of mitochondria in DBA/2 RGC axons suggest reduced potential for fusion and/or incidence of fission events within the mitochondrial population. This lower dynamism could significantly impact RGC axon response to stress.
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