Low-level gestational lead exposure increases retinal progenitor cell proliferation and rod photoreceptor and bipolar cell neurogenesis in mice.
Giddabasappa-A; Hamilton-WR; Chaney-S; Xiao-W; Johnson-JE; Mukherjee-S; Fox-DA
Environ Health Perspect 2011 Jan; 119(1):71-77
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, approximately 25 and approximately 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.
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
Donald A. Fox, Ph.D., University of Houston, College of Optometry, 4901 Calhoun Road, Houston, TX 77204-2020
Environmental Health Perspectives