Part of the National Eye Institute (NEI) Audacious Goals Initiative (AGI) project

“Vision loss is among the top ten disabilities in the United States. Retinal photoreceptors are the main retinal cell types and responsible for directly detecting light. These cells degenerate in a broad range of blinding diseases, including Leber’s congenital amaurosis, retinitis pigmentosa and macular degeneration. Currently, there are no effective cures for any of these diseases. One of the most promising therapies is to reprogram a cell type, called Müller glia, that is already resident in the retina to replace retinal neurons lost to diseases. Zebrafish have the ability to completely regenerate photoreceptors following injury from Müller glia.  Chick Müller glia show a limited regenerative ability while mice, like humans, have completely lost the ability to regenerate retinal neurons. We aim to identify gene regulatory networks that control the ability of Müller glia to give rise to retinal neurons following injury. In collaborations with several labs, we have conducted a comprehensive and unbiased, comparative analysis of gene expression and chromatin conformation by scRNA-seq/bulk-RNA-seq and ATAC-seq in isolated retinal progenitors and Müller glia in zebrafish, chick, and mouse retinas during both development and injury. We have identified a large number of genes that are turned on or off following injury in all three species. These genes are excellent candidates for respectively promoting or inhibiting the ability of retinal glia to give rise to neurons following injury. We up or down-regulate different combinations of these candidate genes that enable mammalian Müller glia to regenerate retinal neurons that have been lost due to various diseases.”