Histone deacetylase inhibition-mediated differentiation of RGC-5 cells and interaction with survival

PURPOSE. The acetylation state of histones is modulated by historic deacetylase (HDAC) and histone acetyltransferase and is an important component in regulating gene transcription, including neuronal differentiation. The authors studied the relationship between histone acetylation and the differentiation and survival of the RGC-5 cell line and compared it with nontranscriptional-dependent differentiation with staurosporine. METHODS. The retinal ganglion cell line RGC-5 was treated with trichostatin A (TSA), other HDAC inhibitors, and staurosporine, differentiation, neuritogenesis, neurotrophic factor dependence, and dependence on RNA transcription were assessed. RESULTS. TSA caused significant differentiation and neuritogenesis. Differences between HDAC inhibition and staurosporine differentiation included the proportion of differentiated cells, cell viability, cell morphology, and transcriptional dependence. HDAC inhibition, but not staurosporine differentiation, resulted in RGC-5 cells that were neurotrophic factor dependent. CONCLUSIONS. These results implicate two different mechanisms for RGC-5 differentiation, with a common downstream effect on neurite outgrowth but a differential effect on neurotrophic factor dependence.