Rod-Shaped Eye Cells Die When Exposed to Lead

Donald A. Fox, University of Houston College of Optometry and
Mark H. Ellisman, University of California, San Diego
R01ES12482 and P42ES10337

Background: Some health effects of lead, cognitive and behavioral impairments, high blood pressure, and kidney disorders, are well known and documented. However, the effects lead has on rod-shaped photoreceptor cells, or rods, of the retina are not well or frequently studied. Rods assist in seeing in dim light. The other type of retinal cells, cones, are responsible for color and spatial vision. Cones are used primarily in daylight and for activities such as reading. A person can lose up to 20% of their rods and not experience any functional loss of vision. However, for people who need to see clearly at night or for people who are losing their rods due to disease or injury, finding a way to prevent the rods from dying could be critical.

The results of a previous research project conducted by this research team demonstrated that 7-10 year-old children whose mothers had elevated levels of lead in their blood during the first trimester of pregnancy developed retinal abnormalities. It isn't clear whether the children's rods are dying, but there are unique abnormalities in the children. These researchers continued their studies by examining the retinas of lead-exposed mice.

Advance: The animal study demonstrated that the rods died from lead-induced apoptosis. Lead triggers an increase in calcium entering the mitochondria, which in turn induces the production of Bax, a "death factor" protein. Bax then causes the release of cytochrome C, which initiates DNA damage and subsequent cell death. Electron micrographs confirmed that more gates or contact sites, thought to be associated with cytochrome C release, were open in cells of the eyes from the lead-exposed mice. Other studies found that an excess of an anti-death protein called Bcl-xL completely blocked the death of the rod cells and maintained normal mitochondrial function in the rods throughout adulthood.

Implication: Over expression of Bcl-xL prevented the effects of Bax and reduced the formation of contact sites preventing the release of cytochrome C. For people losing rods because of retinitis pigmentosa, diabetes, or traumatic injury, finding a way to increase the concentration of Bcl-xL or a similar factor in the eye could prevent cell death.

Citation: He L, Perkins GA, Poblenz AT, Harris JB, Hung M, Ellisman MH, Fox DA. Bcl-xL overexpression blocks bax-mediated mitochondrial contact site formation and apoptosis in rod photoreceptors of lead-exposed mice. Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1022-7.