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S. Y. Chaney, A. Giddabasappa, J. E. Johnson, D. A. Fox; Gestationally Lead-Exposed Mice With Increased Rods and Bipolar Cells Exhibit Late-Onset Rod and Bipolar Cell Degeneration. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3619.
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© ARVO (1962-2015); The Authors (2016-present)
Previously we reported that gestational lead exposure (GLE) increased and prolonged the proliferation of retinal progenitor cells resulting in a 25% increase in the number of late-born rods and bipolar cells in 2 month (m) old mice, with no change in the number of cone, horizontal, amacrine, Müller glial or ganglion cells [ARVO 2007]. GLE also produced late-onset obesity in year-old mice [Leasure et al., EHP 2008], suggesting that age-related alterations may occur in the retina. Thus, our present goal was to examine and compare the retinal morphology in young and aging control and GLE mice.
C57BL/6 female mice were exposed to water or 55 ppm lead solution throughout gestation and until postnatal day 10: equivalent to human gestation period. Fixed-frozen vertical sections from central retina of 2, 12 and 15m animals were stained and processed for immunohistochemistry using nuclear stains [DAPI or Draq5] and cell specific markers for rods [rhodopsin], cones [M- and S-opsins], horizontal cells [calbindin], bipolar cells [chx10], rod bipolar cells [PKC], Müller glia cells [cyclin D3], and amacrine cells [GAD65, Dab1 or ChAT]. The slides were imaged with epifluorescent and confocal microscopy and analyzed using standard blind-observer stereological techniques.
Control retinas were relatively similar at 2, 12 and 15m. The increased number of rods seen in 2m GLE retinas was lost by 12m. This resulted in an outer nuclear layer (ONL) thickness that was not significantly different from controls at 12 and 15m. The number of cone opsin-positive cells was not different in control or GLE retinas at any age. In GLE retinas at 12 and 15m, the inner nuclear layer was significantly thinner than age-matched controls. The number of chx10-positive bipolar cells, which were increased 25% in 2m GLE retinas, was decreased ~20% in 12 and 15m GLE retinas compared to age-matched controls. The number of rod bipolar cells also decreased in these aged GLE retinas. At 2, 12 and 15m, the number of horizontal, Müller glia, amacrine and ganglion cells was not different in control or GLE mice.
These results indicate that a significant and differential degree of apoptosis occurred in rods and bipolar cells of GLE retinas between 2 and 12m, revealing an increased anterograde retinal degeneration from rods to bipolar cells. Moreover, these findings suggest that children with GLE have an increased risk for age-related retinal degeneration and visual disturbances.
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