Protection of Photoreceptors in a Mouse Model of RP10
Recombinant adeno-associated viral (rAAV) vectors have recently been widely used for the delivery of therapeutic transgenes in preclinical and clinical studies for inherited retinal degenerative diseases. Interchanging capsid genes between different AAV serotypes has enabled selective delivery of transgene into specific cell type(s) of the retina. The RP10 form of autosomal dominant retinitis pigmentosa (adRP) is caused by missense mutations within the gene encoding inosine 5ʹ-monophosphate dehydrogenase type 1. Here, we report that the use of rAAV2/5 vectors expressing shRNA targeting mutant IMPDH1 prevents photoreceptor degeneration, and preserves synaptic connectivity in a mouse model of RP10.
KeywordsToxicity Retina Retinitis
This work was supported by grants from Science Foundation Ireland (G20026); The Health Research Board of Ireland (PRO262001); European Union-RETNET (MRTN-CT-2003-504003); European Union-EviGenoRET (LSHG-CT-2005-512036); The British RP Society and Fighting Blindness Ireland. The authors thank Dr. Sara Bowne (University of Texas, Houston) for providing the IMPDH1 antibody, and Dr. Arpad Palfi (Trinity College Dublin, Ireland) for providing the EGFP Dual-Expression plasmid vector.
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