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Low-level gestational lead exposure increases retinal progenitor cell proliferation and rod photoreceptor and bipolar cell neurogenesis in mice.

Authors
Giddabasappa-A; Hamilton-WR; Chaney-S; Xiao-W; Johnson-JE; Mukherjee-S; Fox-DA
Source
Environ Health Perspect 2011 Jan; 119(1):71-77
NIOSHTIC No.
20037770
Abstract
Background: Gestational lead exposure (GLE) produces novel and persistent rod-mediated ERG supernormality in children and adult animals. Objectives: To utilize 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. Results: Blood [Pb] in control, low-, moderate- and high-dose GLE was < / = 1, < / = 10, ~25 and ~40 µg/dL, respectively, at the end of exposure (postnatal day 10: PN10) and by PN30 all 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, but not Müller glial cells, increased in a nonmonotonic manner by 16-30% in PN60 GLE offspring. Retinal lamination and the rod:cone bipolar cell ratio were not altered. In vivo BrdU pulse-labeling and Ki67 labeling of isolated cells from developing mice showed that GLE increased and prolonged retinal progenitor cell proliferation. TUNEL and confocal studies revealed that GLE did not alter developmental apoptosis or produce retinal injury. BrdU-birthdating and confocal studies confirmed the selective rod and bipolar cell increases and showed that the patterns of neurogenesis and gliogenesis were unaltered by GLE. Conclusions: The 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 since they occurred at clinically relevant blood [Pb] and correspond with the ERG phenotype.
Keywords
Lead-compounds; Animal-studies; Eyes; Eyesight; Visual-perception; Exposure-levels; Neurological-reactions; Cell-alteration; Cell-function; Cellular-reactions; In-vivo-study; Neurotoxicity; Cell-biology; Author Keywords: Lead; gestational exposure; development; retina; proliferation; neurogenesis; rod photoreceptors; bipolar cells; glia; mice
Contact
Donald A. Fox, Ph.D., University of Houston, College of Optometry, 4901 Calhoun Road, Houston, TX 77204-2020
CODEN
EVHPAZ
CAS No.
7439-92-1
Publication Date
20110101
Document Type
Journal Article
Email Address
dafox@uh.edu
Funding Type
Grant
Fiscal Year
2011
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-090168
ISSN
0091-6765
Source Name
Environmental Health Perspectives
State
TX
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