PT - JOURNAL ARTICLE AU - Anastasia S. Yandulskaya AU - Melissa N. Miller AU - Ronak Ansaripour AU - Rebecca L. Carrier AU - James R. Monaghan TI - Regenerating axolotl retinas regrow diverse cell types with modulation by Notch signaling and reconnect to the brain AID - 10.1101/2022.04.28.489898 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.04.28.489898 4099 - http://biorxiv.org/content/early/2022/04/29/2022.04.28.489898.short 4100 - http://biorxiv.org/content/early/2022/04/29/2022.04.28.489898.full AB - Some species successfully repair retinal injuries in contrast to non-regenerative mammalian retina. We show here that the Mexican axolotl salamander regrows its excised retina even in adulthood. During early regeneration, cell proliferation occurred in the retinal pigment epithelium (RPE). All dividing cells expressed Vimentin, and some also expressed Müller glia and neural progenitor cell marker Glast (Slc1a3), suggesting that regeneration is driven by RPE-derived retinal progenitor cells. Bulk RNA sequencing showed that genes associated with the extracellular matrix and angiogenesis were upregulated in early-to-mid retinal regeneration. The fully regenerated retina re-established nerve projections to the brain and contained all the original retinal cell types, including Müller glia. Regeneration of cellular diversity may be modulated by Notch signaling, as inhibiting Notch signaling in early regeneration promoted production of rod photoreceptors. Our study highlights the axolotl salamander as an advantageous model of adult tetrapod retinal regeneration and provides insights into its mechanisms.Summary We demonstrate that adult Mexican axolotl salamanders regenerate retinas after a retinectomy. We also show some cellular and molecular mechanisms that drive axolotl retinal regeneration.Competing Interest StatementThe authors have declared no competing interest.RPEretinal pigment epitheliumONLouter nuclear layerINLinner nuclear layerRGCretinal ganglion cellsOPLouter plexiform layerIPLinner plexiform layerCTBcholera toxin subunit BGFPgreen fluorescent proteinECMthe extracellular matrixIGFinsulin-like growth factorTGF-βtransforming growth factor beta