Abstract
BackgroundNaturally occurring apoptosis is a developmental process that shapes the retina by eliminating overproduced neurons. In the absence of the proapoptotic Bcl-2 family member BAX, developmental apoptosis in the retina is disrupted and extra neurons survive. It is unknown how BAX is activated or if this regulation varies between neuronal types and subtypes. Since the Bcl-2 family members BIM, BID, and BBC3 (PUMA) are powerful direct activators of BAX, we used mice deficient for each of these genes to investigate their importance in developmental apoptosis.ResultsBax deficient mice have an increase in retinal ganglion cells (RGCs), bipolar cells and dopaminergic amacrine cells, but not photoreceptors, horizontal cells or cholinergic amacrine cells. The retinas of adult Bim and Bid deficient mice appeared to have no increase in any retinal cell type. Bbc3 deficient mice, either homozygous or heterozygous for a null allele of Bbc3, had an increase in the same cell types as Bax deficient mice. An analogous result may occur in the brain where, similar to Bax deficient mice, Bbc3 deficient mice have a larger gross brain weight compared to wild type mice. In contrast to its developmental role, BBC3 did not appear to be a primary factor in BAX-dependent axonal injury induced neurodegeneration in adult RGCs.ConclusionThe regulation of BAX activation in the retina appears to be complex, dependent on the developmental stage of the animal, the nature of the insult and even the type of neuron.
Highlights
Apoptosis in the retina has a major role in neuronal development and neurodegeneration
Bid deficiency does not alter retinal cell numbers Neurons in the adult retina reside in three layers of cell bodies: the ganglion cell layer (GCL), inner nuclear layer (INL), and outer nuclear layer (ONL), which are connected by two synaptic layers: the inner plexiform layer (IPL) and the outer plexiform layer (OPL)
Bbc3 deficiency increases neuronal number in the retina BBC3 expression has been reported during the postnatal wave of developmental death in the retina [13]; we examined the Bbc3 null retina to see whether its presence is required for normal retinal development
Summary
Apoptosis in the retina has a major role in neuronal development and neurodegeneration. Even though extensive manipulation of the neurotrophic deprivation pathway affected the rate of cell death, it did not alter the final number of RGCs [4,5,6]. To date it is unclear what molecular. In the absence of the proapoptotic Bcl-2 family member BAX, developmental apoptosis in the retina is disrupted and extra neurons survive. It is unknown how BAX is activated or if this regulation varies between neuronal types and subtypes. Since the Bcl-2 family members BIM, BID, and BBC3 (PUMA) are powerful direct activators of BAX, we used mice deficient for each of these genes to investigate their importance in developmental apoptosis
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