Lithium Affects Histogenesis of Embryonic Chick Retina

BACKGROUND: Lithium, a drug used extensively for treatment of bipolar disorders, has also been shown to be neuroprotective in vivo and in vitro. While gross teratogenic effects of lithium at higher doses have been reported, in view of its potential wider use, it is necessary to investigate its effects on tissue formation at relatively low doses of lithium where no apparent teratogenic effects on morphology are observed. MATERIALS AND METHODS: We have used retina of chick embryo to investigate its effects during neural histogenesis. Three major cellular events involved in retinal histogenesis have been monitored: Proliferation as measured by expression of proliferating cell nuclear antigen (PCNA); initiation of differentiation as observed by expression of p27/Kip1 expression; apoptosis as monitored by TdT-mediated dUTPX-nick end labeling. RESULT: We demonstrate that lithium at a dose of 60 mM has no effect on gross eye morphology; it disrupts histogenesis of chick retina by blocking proliferation, inducing apoptosis, and generating post mitotic cells prematurely.