Active DNA demethylation is upstream of rod photoreceptor fate determination and required for retinal development [Human RNA-Seq]

The goal of this study is to investigate the role of TET enzyme-mediated DNA demethylation on retinal development and cell fate specification. We utilized an allelic series of TET enzyme retinal conditional mouse mutants using the Chx10-Cre-GFP transgene, removing the TET enzymes from retinal progenitor cells. We observe that inhibition of DNA demethylation results in abnormal retinal development and a loss of visual function. As human retinoblastoma displays reduced TET3 protein expression and a reduction in 5hmC similar to our TET mutant models, we compare the RNA expression changes across human retinoblastoma and TET mutant retinas to identify common pathways that are altered when 5hmC is lost. Overall design: RNA-sequencing to perform gene expression patterns in human retinoblastoma samples compared to unaffected human control retinas. 3 retinoblastoma cases and 2 control retinal samples were obtained from a retrospective search of pathology archive records. Tissue blocks were sectioned and RNA isolated from dissected regions of tumor or unaffected retina.