Congenital retina abnormalities such as retinal degenerative diseases cause varying degrees of irreversible vision loss in millions of people worldwide. Although recent advances in our understanding of retinal development have facilitated the use of screening protocols to detect mutations in genes associated with those ocular diseases, no therapeutic approach is yet available. A conserved network of transcription factors is essential for eye formation. The homeobox-containing gene Six3 is one of the members of that complex network that regulates visual system development. Conditional removal of Six3 from the developing mouse eye field is sufficient to arrest NR specification;a result demonstrating the critical role of Six3 during vertebrate retina development. The work proposed in this application builds on our previous findings and our generated mouse models to expand our knowledge about the processes leading to the formation of the visual system.
Recent advances using embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) suggest that one day cell-replacement therapy will be used to treat these ocular diseases. A prerequisite to achieving this goal is to better understand the regulatory cascades and signaling pathways that control normal retina development. This knowledge will help us to better understand the pathogenesis of ocular diseases and provide the essential framework necessary to design approaches that will facilitate future efforts aimed toward controlling the differentiation of ESCs and iPSCs, in vivo and in vitro, into retina cells.
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