Histone deacetylase 4 (HDAC4) shuttles between the nucleus and cytoplasm, and serves as a nuclear corepressor that regulates bone and muscle development. We report that HDAC4 regulates the survival of retinal neurons in the mouse in normal and pathological conditions. Reduction in HDAC4 expression during normal retinal development led to apoptosis of rod photoreceptors and bipolar (BP) interneurons, whereas overexpression reduced naturally occurring cell death of the BP cells. HDAC4 overexpression in a murine model of retinal degeneration prolonged photoreceptor survival. The survival effect was due to the activity of HDAC4 in the cytoplasm, and relied at least in part upon the activity of hypoxia inducible factor 1α (HIF1α). These data provide evidence that HDAC4 plays an important role in promoting the survival of retinal neurons.
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