AAV-mediated delivery of ciliary neurotrophic factor prolongs photoreceptor survival in the rhodopsin knockout mouse

Retinitis pigmentosa (RP), an inherited retinal degenerative disease causin g blindness, is characterized by progressive apoptotic death of photorecept ors. Therapeutic modification of photoreceptor apoptosis may provide an eff ective therapy for this disorder. Ciliary neurotrophic factor (CNTF) has be en shown to promote survival of a number of different neuronal cell types, including photoreceptors. The present study aimed to test whether adeno-ass ociated virus (AAV)-mediated delivery of the gene encoding CNTF delays phot oreceptor death in the rhodopsin knockout (opsin(-/-)) mouse, an animal mod el of RP. The vector was made to express a secretable form of CNTF in tande m with a marker GFP. Cultured 293 cells transduced with this virus expresse d both CNTF and GFP. The conditioned media from such cells supported the su rvival of chick dorsal root ganglion neurons in the same manner as recombin ant CNTF. Subretinal administration of this virus led to efficient transduc tion of photoreceptors as indicated by GFP fluorescence and CNTF immunostai ning. Histologic examination showed significant photoreceptor preservation in the injected quadrant of the retina. This protection lasted through term ination of the experiment (3 months). AAV-mediated delivery of CNTF may hav e implications for the treatment of human retinal degeneration.