Molecular basis of retinal remodeling in a Zebrafish model of Retinitis Pigmentosa

A hallmark of inherited retinal degenerative diseases such as Retinitis Pigmentosa (RP) is progressive structural and functional remodeling of the remaining retinal cells as photoreceptors degenerate. Extensive remodeling of the retina stands as a barrier for the successful implementation of strategies to restore vision. To understand the molecular basis of remodeling, we performed analyses of single-cell transcriptome data from adult Zebrafish retina of wild-type and a P23H mutant rhodopsin transgenic model of RP with continuous degeneration and regeneration. We provide a benchmark atlas of retinal cell type transcriptomes in Zebrafish and find changes in all retinal cell types in the P23H model. These include widespread oxidative stress, changes in reliance on oxidative metabolism and glycolysis, widespread synaptic remodeling, and changes in circadian rhythm regulation. This comprehensive transcriptomic analysis provides a molecular road map to understand how the retina remodels in the context of chronic retinal degeneration with ongoing regeneration. We have performed single-cell RNA Sequencing (sc-RNA Seq) of adult retina to assess the transcriptomic remodeling that takes place in the P23H Zebrafish model. In addition to providing a benchmark atlas of retinal cell type transcriptomes in the wild-type adult Zebrafish retina, we find transcriptional changes in essentially all cell types, reflective of the remodeling that has gone on in the chronic disease.