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J.E. Johnson, Jr., G.A. Perkins, J. Brown, P. Lahsaei, S. Ghassemzadeh, M.H. Ellisman, D.A. Fox; A Three–Dimensional Electron Tomographic Analysis of Rod Photoreceptor Synaptic Terminal Mitochondria in Control, Lead–Exposed, and/or Bcl–xL Transgenic Mice . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2852.
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© ARVO (1962-2015); The Authors (2016-present)
Previously we characterized and compared mitochondrial cristae topography and connectivity, matrix volume and contact sites of rod and cone inner segments (RIS & CIS) from wild–type C57BL/6 mice. Since postnatal lead exposure produces rod–selective apoptosis, we also examined RIS mitochondria from wild–type and transgenic mice overexpressing Bcl–xL in photoreceptors (Tg) exposed to either water or lead (Pb) solution during postnatal development. The overall goal of the present study was to similarly characterize the mitochondria in synaptic terminals (ST) of wild–type rods (spherules) and cones (pedicles) and in rod spherules of wild–type and Tg mice exposed to either water or Pb solution during postnatal development and then to compare the respective mitochondrial ST and IS results.
Newborn wild–type or Tg mice were raised by dams drinking water (Con) or Pb solution throughout lactation. Laser scanning confocal microscopy, electron microscopy and three–dimensional electron tomography studies used 21 or 60 day old retinas from all four groups: Con, Tg, Pb and Tg+Pb.
All spherules had one large mitochondrion compared to ∼5 per RIS, while pedicles had 3–5 mitochondria compared to ∼10 per CIS. Spherule and pedicle cristae were mostly tubular, however, the abundance of cristae membranes was smaller in pedicles. Bcl–xL localized to inner segment and synaptic terminal mitochondria. The mitochondria crista junction (CJ) diameters in spherules of Con, Tg and Tg+Pb mice were smaller than those in RISs and were further decreased in Pb mice. The mitochondria CJ diameters in wild–type pedicles were also smaller than in CISs. Spherule mitochondria in Pb mice had increased matrix volumes, whereas there were no lead–induced changes in matrix volume or CJ size in RIS mitochondria.
Our results reveal striking compartmental differences between inner segment and synaptic terminal mitochondria of rods and cones in wild–type mice, and between RIS and spherule mitochondria in postnatally lead–exposed mice. Consistent with our earlier work on RISs, Bcl–xL prevented the Pb–induced rod–selective alterations in spherule mitochondria: most likely by blocking the transition pore. These findings have relevance for photoreceptor synaptic bioenergetics and transmitter release, expand lead’s retinal sites of action, and have relevance for therapies in mitochondrially–mediated neurodegeneration.
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