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Rajesh C. Rao, Muhammad Taimur A. Malik, Dong Feng Chen; Epigenetic Regulation Of Muller Glial Cell And Retinal Progenitor Cell Survival And Proliferation By Histone Methyltransferases. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5418.
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© ARVO (1962-2015); The Authors (2016-present)
Histone methyltransferases (HMTases) catalyze lysine (K) methylation (HKM) marks on histone tails and represent an important epigenetic mechanism that establishes cell-specific gene expression and functions in development. However, epigenetic control of retinal development is poorly understood. This study was conducted to assess the functional roles of HMTases in murine retinal cells in vitro.
Muller glia and retinal progenitor cells were isolated from perinatal and early postnatal murine retina and cultured in the presence of small-molecule inhibitors against the HMTases Ezh2 and G9a. To assess the role of Ezh2 and G9a in these populations of retinal cells, TUNEL and anti-BrdU staining were used to determine the levels of proliferation and apoptosis in inhibitor-treated and control retinal cell cultures.
Inhibition of Ezh2 and G9a by small-molecule antagonists induced Muller glial cell apoptosis. Furthermore, HMTase blockade impaired proliferation of Muller cells. Ezh2 and G9a were also found to regulate viability and mitotic activity of retinal progenitor cells.
Epigenetic regulation of gene transcription by Ezh2 and G9a mediated HKM is required for Muller glial cell survival and proliferation. Muller glia proliferation is associated with retinal detachment, epiretinal membrane, geographic atrophy and retinal degenerations. Moreover, Muller glia have been reported to possess progenitor cell properties with the capacity for neuronal differentiation, and may be a source for endogenous repair in neurodegeneration. Therefore Ezh2 and G9a may represent targets to modulate Muller glial cell proliferation and survival in a variety of retinal disorders.
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