December 2002
Volume 43, Issue 13
ARVO Annual Meeting Abstract  |   December 2002
Bcl-xL Inhibits Lead and Calcium-Induced Rod Apoptosis by Blocking the Increase in Mitochondrial Contact Sites
Author Affiliations & Notes
  • DA Fox
    Univ Houston Houston TX
  • GA Perkins
    UCSD San Diego CA
  • L He
    UNC Chapel Hill NC
  • AT Poblenz
    UT MD Anderson Houston TX
  • MH Ellisman
    UCSD San Diego CA
  • JB Harris
    Univ Houston Houston TX
  • Footnotes
    Commercial Relationships   D.A. Fox, None; G.A. Perkins, None; L. He, None; A.T. Poblenz, None; M.H. Ellisman, None; J.B. Harris, None. Grant Identification: Support: ES03183;EY07088;RR04050;NS14718;KD54441
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 1887. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      DA Fox, GA Perkins, L He, AT Poblenz, MH Ellisman, JB Harris; Bcl-xL Inhibits Lead and Calcium-Induced Rod Apoptosis by Blocking the Increase in Mitochondrial Contact Sites . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1887.

      Download citation file:

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

  • Supplements

Abstract: : Purpose: Photoreceptor apoptosis and visual deficits occur in man and animals with inherited and chemical-induced retinal degenerations, and retinal diseases and injuries. Rod-selective apoptosis is produced by developmental lead exposure in mice and by in vitro lead and/or calcium. The latter activates the cytochrome c-caspase cascade of apoptosis. Methods: This study used wild-type and transgenic mice overexpressing Bcl-xL in photoreceptors to examine the role of mitochondria in lead-induced rod apoptosis. Newborn mice were raised by dams drinking water (controls) or 0.15% lead acetate solution. At weaning, studies of rod mitochondria were conducted in all four groups (control, Bcl-xL, Lead, Bcl-xL/Lead) using three-dimensional electron microscopic tomography, JC-1 staining, immunoblots for cytochrome c, caspase assays and oxygen consumption. Results: There were no differences between the four treatment groups for 5 of 7 different measurements of rod mitochondrial substructures (crista widths, crista junction diameters, outer (OMM)-inner membrane widths, contact site widths, contact site diameters). In contrast to the in vitro lead and/or calcium results, no physical disruptions of the OMM or swollen mitochondrial matrices were observed. Lead-induced rod apoptosis was accompanied by calcium overload, increases in mitochondrial contact site area and density, decreases in rod mitochondrial respiration and membrane potential (depolarization), cytochrome c release and caspase activation. Bcl-xL overexpression completely blocked the lead-induced increase in contact sites and all apoptotic events, except calcium overload, and maintained normal rod respiration. Conclusion: These results suggest that Bcl-xL is located and functions at mitochondrial contact sites to block the opening of the permeability transition pore and to maintain normal rod function. These findings have relevance for pharmacological and gene therapies in human and animal retinal and neuronal degenerations where lead exposure, calcium overload and/or mitochondrial dysfunction occur.

Keywords: 341 cell death/apoptosis • 475 mitochondria • 334 calcium 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.