This paper is the result of a collaborative effort between Bryan William Jones, Mineo Kondo and Hiroko Terasaki, Carl Watt, Kevin Rapp, James Anderson, Yanhua Lin, Maggie Shaw, Jia-Hui Yang and Robert Marc.
This work presents a substantial advance in models of Retinitis pigmentosa (RP), an set of inherited blinding diseases characterized by progressive loss of retinal photoreceptors. Getting tissues from human subjects with RP is rare, so transgenic models of retinal degenerative diseases are desirable. While there are numerous rodent models of retinal degeneration, most are poor platforms for interventions that can translate into clinical practice. In contrast, the rabbit possesses a number of desirable qualities for a model of retinal disease including a large eye and an existing and substantial knowledge base in retinal circuitry, anatomy and ophthalmology. This study encompassed the analysis of degeneration, retinal remodeling and neural reprogramming in a rabbit model of retinal degeneration, created by Mineo Kondo and Hiroko Terasake at the University of Nagoya which expresses a rhodopsin proline 347 to leucine transgene in a TgP347L rabbit as a powerful model to study the pathophysiology and treatment of retinal degeneration. This manuscript shows that disease progression in the TgP347L rabbit closely mimics human cone-sparing RP, including the cone-associated preservation of bipolar cell signaling and triggering of reprogramming. The relatively fast disease progression makes the TgP347L rabbit an excellent model for gene therapy, cell biological intervention, progenitor cell transplantation, surgical interventions and bionic prosthetic studies.