Rod Photoreceptor Regeneration in a Zebrafish Model with Retinitis Pigmentosa

A cellular hallmark of inherited retinal degenerative diseases is progressive loss of photoreceptors until one is completely blind. Unlike mammalian models, Zebrafish have the ability to naturally regenerate their neurons after injury or disease is detected. We have generated a zebrafish model with the most common autosomal dominant form of the inherited retinal degenerative disease known as Retinitis Pigmentosa. We utilize immunohistochemistry, single-cell RNA sequencing, several analysis tools, behavioral assays and oligonucleotides to characterize our zebrafish model and identify the transcription factors necessary for rod photoreceptor regeneration. We show that our zebrafish model has continuous degeneration and regeneration of rod photoreceptors throughout its entire life, maintains a retinal environment characteristic of early stages of Retinitis Pigmentosa, and has behavioral deficits caused by the loss of rods. Finally, we identify and validate genes that play an important role in the proliferation of progenitor cells, differentiation of progenitor cells into rod photoreceptors, maturation, and integration of these rod photoreceptors. Future studies will continue to investigate the mechanism by which newly formed rods are able to integrate into the retina. These findings will be vital for therapeutic strategies trying to restore vision to the blind.