Retinal Remodeling in the Tg P347L Rabbit, a Large-Eye Model of Retinal Degeneration

JCN P347

This paper (we got the cover) (pdf here) is the result of a collaborative effort between myself, Mineo Kondo and Hiroko Terasake, 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.  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.  For this study, we analyzed degeneration, remodeling and 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.  We show 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.

This model also represents the core of our future work in the next grant cycle for therapies of retinal degenerative disease and we are tremendously excited for the future.  In fact, the details will have to wait for later, but I have not been this optimistic for a true cure for blindness since I started my career in science.  The implications for all those suffering from blinding disease is substantial and we are working aggressively to make this happen.  Wish us all sighted and visually impaired, good fortune on this journey over the next few years.




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