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M. Donovan, F. Doonan, T.G. Cotter; Investigation of the Role of Bim in Apoptosis During Retinal Development and Degeneration . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4854.
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To investigate the role of Bim as a regulator of apoptosis during development and degeneration of the mouse retina.
Cell death was analyzed by TUNEL during postnatal development (postnatal day 2, 5, 8, 13 and 60) in wild type and Bim–/– mice and following ionophore treatment of retinal explants. Immunohistochemistry (IHC) was employed to detect caspase–9 and caspase–3 cleavage. Expression of pro–apoptotic Bim during photoreceptor apoptosis in retinal explants and during development was analysed by western blot.
We show that the waves of postnatal cell death that eliminate rod photoreceptors, bipolar cells, Muller glia and ganglion cells are significantly delayed in the retinas of Bim–/– mice indicating that this protein is important but perhaps not essential for retinal development. Importantly, we demonstrate that the expression of BimEL decreases markedly during postnatal development and retinal explant cultures exposed to calcium stress must re–express Bim for caspase activation and photoreceptor apoptosis to occur. Finally, we demonstrate that Bim–/– retinal explants treated with various death stimuli have significantly reduced photoreceptor apoptosis compared to their wild type counterparts.
Bim deletion produces only a transient delay in developmental retinal apoptosis in this study indicating that Bim and other ‘BH3–only’ proteins may perform a partially redundant role upstream of cytochrome–c release during retinal development. In contrast, Bim appears to play an essential role in pathological apoptosis in retinal explant cultures treated with various death stimuli.
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