HDAC4 Regulates Neuronal Survival in Normal and Diseased Retinas
Bo Chen and
Constance L. Cepko
Histone deacetylase 4 (HDAC4) shuttles between the nucleus and
cytoplasm and serves as a nuclear co-repressor 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 mouse model of retinal degeneration prolonged photoreceptor
survival. The survival effect was due to the activity of HDAC4
in the cytoplasm and relied at least partly on the activity
of hypoxia-inducible factor 1
(HIF1
). These data provide evidence
that HDAC4 plays an important role in promoting the survival
of retinal neurons.
