Abstract
Purpose :
Mutations in cyclic nucleotide gated channel subunit alpha 1 (CNGA1) have been reported to cause autosomal recessive retinitis pigmentosa. There are no gene therapy approaches for CNGA1-RP. Here, we intended to develop a gene augmentation therapy by means of subretinal delivery of recombinant adeno-associated viral (AAV) vectors in the CNGA1 knockout (CNGA1-/-) mouse model.
Methods :
We injected postnatal (P) day 14 CNGA1-/- mice subretinally with either AAV8-CNGA1 or balanced salt solution (BSS). Three months after injection, the transgene proteins were examined by western blot and immunofluorescence. Fundus photography and optical coherence tomography (OCT) were used to observe the fundus and retina structure. And electroretinogram (ERG) responses were performed to evaluate the rod and cone functions of CNGA1 KO mice.
Results :
Three months after injection, we found that subretinal injection of AAV8-CNGA1 resulted in the efficient expression of CNGA1 in rod out segment, a significant retinal morphological preservation, and a recovery of rod-driven function in CNGA1 KO mice.
Conclusions :
These results demonstrated the efficiency of AAV8-CNGA1 gene augmentation therapy in CNGA1 KO mice, which provides a proof-of-concept for the treatment of CNGA1-RP.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.