Histone Deacetylase 4 Plays Role in Retina
Overexpression in a mouse model of retinal degeneration increased photoreceptor survival
MONDAY, Jan. 12 (HealthDay News) -- Histone deacetylase 4 (HDAC4) influences the survival of mouse retinal neurons, and a drop in expression during retinal development leads to apoptosis of rod photoreceptors and bipolar interneurons, according to research published in the Jan. 9 issue of Science.
Bo Chen, Ph.D., and Constance L. Cepko, Ph.D., of Harvard Medical School in Boston, transfected a plasmid with a short hairpin RNA directed to HDAC4 into newborn mice's retinas via electroporation, with results indicating that HDAC4 was necessary for cell survival. Cells receiving the HDAC4 short hairpin RNA died from apoptosis.
Overexpression of HDAC4 in newborn mice's retinas led to more bipolar cells in the upper inner nuclear layer, indicating that HDAC4 may protect bipolar cells from apoptosis, the researchers report. Electroporating pCAG-HDAC4 or pCAG-HDAC6 into the newborn rd1 mouse model of retinal degeneration led to the finding at day 50 that retinas overexpressing HDAC4 had many rods, but those overexpressing HDAC6 did not. Also, in the photoreceptors of the rd1 retina, expression of HDAC4 but not HDAC6 led to the detection of hypoxia-inducible factor 1α (HIF1α), the investigators found.
"In the mouse retina, HDAC4 has an essential role in neuronal survival. From a therapeutic perspective, HDAC4 prolonged photoreceptor survival in mice undergoing retinal degeneration. HDAC6 did not lead to increased abundance of HIF1α protein or promote rod survival in mice, although it rescued degeneration in Drosophila. Therefore, more than one pathway for neuronal survival may be regulated by HDACs," the authors conclude.
This research was supported in part by Merck, and the authors have filed a patent application based on the work.