Low-Level Gestational Lead Exposure Increases Retinal Progenitor Cell Proliferation and Rod Photoreceptor and Bipolar Cell Neurogenesis in Mice

Abstract

BackgroundGestational lead exposure (GLE) produces novel and persistent rod-mediated electroretinographic (ERG) supernormality in children and adult animals.ObjectivesWe used our murine GLE model to test the hypothesis that GLE increases the number of neurons in the rod signaling pathway and to determine the cellular mechanisms underlying the phenotype.ResultsBlood lead concentrations ([BPb]) in controls and after low-, moderate-, and high-dose GLE were ≤ 1, ≤ 10, approximately 25, and approximately 40 μg/dL, respectively, at the end of exposure [postnatal day 10 (PND10)]; by PND30 all [BPb] measures were ≤ 1 μg/dL. Epifluorescent, light, and confocal microscopy studies and Western blots demonstrated that late-born rod photoreceptors and rod and cone bipolar cells (BCs), but not Müller glial cells, increased in a nonmonotonic manner by 16–30% in PND60 GLE offspring. Retinal lamination and the rod:cone BC ratio were not altered. In vivo BrdU (5-bromo-2-deoxyuridine) pulse-labeling and Ki67 labeling of isolated cells from developing mice showed that GLE increased and prolonged retinal progenitor cell proliferation. TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) and confocal studies revealed that GLE did not alter developmental apoptosis or produce retinal injury. BrdU birth-dating and confocal studies confirmed the selective rod and BC increases and showed that the patterns of neurogenesis and gliogenesis were unaltered by GLE.ConclusionsOur findings suggest two spatiotemporal components mediated by dysregulation of different extrinsic/intrinsic factors: increased and prolonged cell proliferation and increased neuronal (but not glial) cell fate. These findings have relevance for neurotoxicology, pediatrics, public health, risk assessment, and retinal cell biology because they occurred at clinically relevant [BPb] and correspond with the ERG phenotype.

High lead exposure is associated with telomere length shortening in Chinese battery manufacturing plant workers

“…However, it has been reported that steel workers with short-term metal-rich particulate matter exposure within a week's duration had longer telomere length compared with baseline samples 31. Similarly, it has been recently demonstrated that low-level lead exposure could increase and prolong retinal progenitor cell proliferation, rather than apoptosis 32. Although our finding suggests that Pb at a certain level in blood (short-term Pb exposure) may increase telomere length, since BLB (β=−1.72) played a predominant effect on PWBTL, and the inpatient workers showed relatively high long-term Pb exposure doses, it would not be surprising that comprehensive consequence of lead exposure in the battery plant workers was telomere length shortening.…”

Dry eye modulates the expression of toll-like receptors on the ocular surface

“…The membranes were probed with anti-TLR4 (0.2 μg/ml, Santa Cruz Biotechnology) or anti-TLR9 (1 μg/ml, AbCam; Cambridge, MA) antibodies, then incubated with horseradish peroxidase-conjugated secondary antibody, and visualized with ECL Plus (GE Healthcare; Piscataway, NJ). The membranes were stripped and reprobed using a GAPDH antibody as previously described (Giddabasappa et al, 2011). Densitometry measurements were obtained from non-saturated blots and the pixel intensity was normalized to GAPDH.…”

Dynamics of the Rhomboid-like Protein RHBDD2 Expression in Mouse Retina and Involvement of Its Human Ortholog in Retinitis Pigmentosa

“…Immunostaining of Mouse Retinal Sections-All tissue processing, image acquisition, and analysis procedures were as described (23)(24)(25). Central sections (10 m thick; three nonadjacent sections per slide) were located 200 -400 m from the optic nerve.…”