![]() ![]() As a window onto the molecular basis of remodeling, we have performed a comparative analysis of single-cell transcriptome data from adult Zebrafish retina of wild-type and a P23H mutant rhodopsin model of RP. While many studies focus on regenerative or bionic therapies to restore vision, extensive remodeling of retinal cell types throughout the course of retinal degenerative diseases stands as a barrier for successful implementation of these strategies. A hallmark of these diseases is progressive structural and functional remodeling of the remaining retinal neurons as rod photoreceptors are lost. Inherited retinal degenerative diseases such as Retinitis Pigmentosa (RP) result in progressive loss of photoreceptors until an individual is completely blind. This transgenic fish will provide a useful model system to study rod photoreceptor regeneration and integration. There was a modest remodeling of bipolar and Müller glial cells. Adult fish displayed ongoing apoptotic cell death in the ONL and an abundance of proliferating cells, predominantly in the ONL. Adult fish displayed thinning of the outer nuclear layer (ONL) and loss of rod outer segments, but retained a single, sparse row of rods. Rods expressing the mutant rhodopsin formed very small or no outer segments and the mutant protein was delocalized over the entire cell. P23H transgenic fish expressed the transgene in rods from 3 days post fertilization onward. Adult and juvenile fish were examined by immunofluorescence, TUNEL and BrdU incorporation assays. ![]() We used Tol2 transgenesis to express mouse rhodopsin carrying the P23H mutation and an epitope tag in zebrafish rod photoreceptors. As a step toward investigating regenerative therapies, we developed a zebrafish model of Retinitis Pigmentosa that displays ongoing regeneration. Regenerative therapies offer some hope, but their development is challenged by the limited regenerative capacity of mammalian model systems. More than 1.5 million people suffer from Retinitis Pigmentosa, with many experiencing partial to complete vision loss.
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