May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Differential Susceptibility of Cone Photoreceptor Synaptic and Non-Synaptic Mitochondria to Postnatal Lead Exposure and Protection by Bcl-xL
Author Affiliations & Notes
  • D. A. Fox
    University of Houston, Houston, Texas
  • G. A. Perkins
    University of California, San Diego, California
  • J. E. Johnson
    University of Houston-Downtown, Houston, Texas
  • R. T. Scott
    University of California, San Diego, California
  • P. Poquiz
    University of California, San Diego, California
  • J. Kim
    University of California, San Diego, California
  • M. H. Ellisman
    University of California, San Diego, California
  • Footnotes
    Commercial Relationships  D.A. Fox, None; G.A. Perkins, None; J.E. Johnson, None; R.T. Scott, None; P. Poquiz, None; J. Kim, None; M.H. Ellisman, None.
  • Footnotes
    Support  NIH Grants ES012482, EY07024, EY07088, RR04050 and NS14718.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3007. doi:
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    • Get Citation

      D. A. Fox, G. A. Perkins, J. E. Johnson, R. T. Scott, P. Poquiz, J. Kim, M. H. Ellisman; Differential Susceptibility of Cone Photoreceptor Synaptic and Non-Synaptic Mitochondria to Postnatal Lead Exposure and Protection by Bcl-xL. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3007.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Rod-selective apoptosis and scotopic-mesopic vision deficits are produced by postnatal lead exposure (PLE) in man and experimental animals. Rod, but not cone, inner segment (RIS; CIS) mitochondria (Mt) are the primary target site of action. Previously we showed that rod spherule and RIS Mt are both targets of PLE, but that Bcl-xL only protected the RIS Mt from persistent structural and functional deficits [ARVO 2007]. The goal of these experiments was to conduct similar experiments for cone pedicle and CIS Mt.

Methods: : Newborn C57BL/6 mice were raised by dams drinking water (Con) or a low-level lead (Pb) solution throughout lactation. To assess pedicle and CIS Mt ultrastructural and substructural differences as well as vulnerability to PLE, we used wild-type and transgenic mice that overexpressed Bcl-xL in rod and cone synaptic terminal and IS Mt (Tg). The results are compared to our control cone Mt findings [Mol Vis 2003; 2007]. Immunocytochemistry and confocal microscopy, electron microscopy, and three-dimensional electron tomography studies used adult retinas from all four groups: Con, Tg, Pb and Tg+Pb.

Results: : Molecular markers of Mt compartments revealed retinal lamination and cellular localization of Mt. Cone pedicles had five medium-sized Mt compared to ~10/CIS cross-section. PLE did not affect CIS Mt or the number of pedicle Mt. Pedicle Mt in PLE mice were swollen and they had increased cristae surface area, cristae volume, number of segments per cristae, fraction of cristae segments with multiple cristae, number of cristae segments per volume and crista junction diameter. The number of cristae per unit volume was not affected by PLE. Bcl-xL only protected the PLE-induced increases in cristae surface area and cristae volume. In contrast, persistent increases in the abundance of cristae membrane were found in the pedicle Mt of PLE mice with or with Bcl-xL.

Conclusions: : These results reveal compartmental specific differences in the morphology, substructure, sensitivity and vulnerability of cone pedicle and CIS Mt to PLE and likely other toxicant or inherited insults. The findings indicate that lead produces alterations in cristae fusion-fission and provide new data on cone synaptic terminal Mt injury in the absence of cone photoreceptor apoptosis. They indicate that persistent structural, and likely functional, alterations of cone and rod synaptic terminals remain even after the rod-selective apoptosis is completely blocked.

Keywords: apoptosis/cell death • mitochondria • photoreceptors 
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