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William D. Ferrell, Shawntay Chaney, Donald A. Fox, Robert E. Marc, Bryan W. Jones; Low-Level Gestational Lead Exposure Induces Metabolomic Changes in Developing Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2688.
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Low-level gestational lead exposure (GLE) increases retinal progenitor cell proliferation and rod photoreceptor and bipolar cell neurogenesis in mice. To determine the GLE-induced changes in cellular metabolism, we surveyed the small molecular metabolic signals in developing control and GLE retinas.
Female C57BL/6 mice were given tap water or water containing 55 ppm lead two weeks before mating, during pregnancy, and through postnatal day (PND)10 to produce a human-equivalent GLE model. Mice were sacrificed between 1000 and 1200 hours on PND2, PND6, PND10, and 4 weeks of age. Retinas were fixed with conventional aldehydes, plastic embedded, sectioned and processed for computational molecular phenotyping (CMP). Sections from control and GLE central retinas were examined and compared.
Consistent with our previous studies, GLE mouse retinas had prolonged development compared to control. Between PND2 and PND10 there were metabolic variances in the molecular signals between GLE and controls for virtually every metabolite and protein examined: GABA, glycine, L-glutamate, L-glutamine, glutathione, arginine, L-aspartate, glutamate synthetase, CRALBP, GFAP, rod opsin and taurine. Notable changes in GLE retinas included an increased level of glutathione and GABA in the differentiated cell layer at PND2; an increased level of glutamate and aspartate, a decreased levels of glutamine and a delay in CRALBP expression in the Müller glial cell endfeet at PND6; and greater spacing between the progenitor cell layer and differentiated cell layer, lowered overall taurine levels, and delayed rhodopsin development at PND10. The most pronounced changes in the 4 week-old GLE retinas included isolated cell classes with higher aspartate, glutamine, glutamate and GABA levels: especially in the GCL.
GLE-induced produced distinct metabolic differences during early postnatal retinal development. Differences in the metabolic envelopes of many retinal cell classes including horizontal cells, bipolar cells, amacrine cells, Müller glial and ganglion cells were observed. These findings suggest that alterations in retinal metabolism and the metabolic signatures of individual retinal cells may underlie the increased and prolonged cell proliferation and maturation of late-born rods and bipolar cells.
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