Ascl1 in Retinal Regeneration: From Neuronal Fate Determination to Reprogramming Mechanisms

Ascl1 has emerged as a key transcription factor of interest in regenerative medicine due to its critical role in retinal neurogenesis and its therapeutic potential in neurological disorders. In lower vertebrates, such as zebrafish, retinal injury induces rapid expression of Ascl1a, enabling Müller glial cells to acquire stem cell-like properties and regenerate retinal neurons. In contrast, mammalian Müller glia do not spontaneously express Ascl1 following injury and lack the capacity for neuronal reprogramming. Exogenous expression of Ascl1 enables the reprogramming of mammalian Müller glia and fibroblasts into functional retinal neurons, underscoring its therapeutic potential in the context of retinal neurodegeneration. In this review, we present a comprehensive overview of Ascl1, focusing on its key role in retinal neuronal development, retinal regeneration, and therapeutic potential in neurodegenerative diseases. Furthermore, we provide a comprehensive overview of the mechanisms underlying Ascl1-mediated retinal regeneration and its multiple regulatory factors, aiming to offer novel insights and a theoretical foundation for future therapeutic strategies targeting retinal neurodegeneration.