HDAC Inhibition Prevents Rd1 Mouse Photoreceptor Degeneration
Acetylation of histones is a posttranslational modification which induces important changes in chromatin structure and transcriptional activity. It is regulated by two classes of enzymes: histone acetyl transferases (HATs) and histone deacetylases (HDACs). While hyperacetylation may enhance expression of transcription factors critical for rod differentiation, in rd1 mouse degenerating photoreceptors, acetylation was found to be dramatically reduced. Decreased acetylation was likely due to overactivation of HDACs, which temporally preceded photoreceptor degeneration. Moreover, inhibition of HDAC activity in rd1 retinal explant cultures decreased activity of poly-ADP-ribose-polymerase (PARP) and strongly reduced cell death. These results propose HDACs as regulators of PARP activity and novel targets for future pharmacological intervention in retinal degeneration.
KeywordsRetinitis pigmentosa HDAC Photoreceptor degeneration rd1 mouse Retinal explant culture Trichostain A Neuroprotection PARP
We thank Beckman, Bernard and Shirlee Brown Glaucoma Lab, Foundation Fighting Blindness, Schneeweiss Stem Cell Fund, Jonas Family Fund, Bernard Becker-Association of University Professors in Ophthalmology-Research to Prevent Blindness (RPB), and EY018213. The Kerstan Foundation and the German research Institute (PA175 1/1–1).
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