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Updated: Aug 6, 2026
Subretinal Injection of Gene Therapy Vectors and Stem Cells in the Perinatal Mouse Eye
Published on: November 25, 2012
Gene augmentation therapy successfully treats mice with complete congenital stationary night blindness (cCSNB),
Nazarul Hasan1,2, Cecilia A Attaway2,3, Mattia Di Paolo2
1Departments of Biochemistry & Molecular Genetics, University of Louisville, Louisville, KY, USA.
Abstract:
Recombinant adeno-associated virus (rAAV) mediated gene therapy is an effective approach for targeting therapeutic genes to retinal photoreceptors. Complete congenital stationary night blindness (cCSNB) is a genetically heterogeneous inherited retinal disease caused by mutations in one of several genes that are part of a large, interdependent depolarizing bipolar cell (DBC) signalplex required for normal synaptic signaling with photoreceptors. These genes include NYX, GRM6, TRPM1, GPR179, and LRIT3, and the resulting cCSNB phenotype is characterized by abnormally low-light vision, myopia, and nystagmus, but does not include retinal degeneration. Because of the non-progressive and recessive nature of cCSNB, we investigated the potential of a gene augmentation approach in the mature retina to improve retinal function and cortical visual acuity. We used a mouse model of cCSNB caused by LRIT3 loss to evaluate the efficacy of a single subretinal injection of an rAAV expressing LRIT3 in either rods or cones, and the extent of restoration of retinal function and visual acuity. We show that gene augmentation by expressing LRIT3 in Lrit3-/- retinas of mature mice restores the DBC synaptic signaling complex and is sufficient to rescue retinal function and improve visual acuity.
Insights
Gene therapy using recombinant adeno-associated virus (rAAV) can restore vision in congenital stationary night blindness (cCSNB). This study shows rAAV-mediated LRIT3 gene augmentation rescues retinal function and visual acuity in a mouse model.
Area of Science:
- Ophthalmology
- Genetics
- Molecular Biology
Background:
- Congenital stationary night blindness (cCSNB) is a group of inherited retinal diseases.
- cCSNB results from mutations in genes crucial for synaptic signaling between photoreceptors and bipolar cells.
- The disease causes poor low-light vision, myopia, and nystagmus without retinal degeneration.
Purpose of the Study:
- To investigate gene augmentation therapy for cCSNB using a mouse model.
- To evaluate the efficacy of restoring LRIT3 gene expression in the mature retina.
- To assess the restoration of retinal function and visual acuity.
Main Methods:
- Utilized a mouse model of cCSNB caused by LRIT3 loss.
- Administered a single subretinal injection of recombinant adeno-associated virus (rAAV) expressing LRIT3.
- Evaluated gene expression in rods and cones, and assessed retinal function and visual acuity.
Main Results:
- Successful restoration of the depolarizing bipolar cell (DBC) synaptic signaling complex in Lrit3-/- retinas.
- Demonstrated that LRIT3 gene augmentation is sufficient to rescue retinal function.
- Showed significant improvement in visual acuity following gene therapy.
Conclusions:
- Recombinant adeno-associated virus (rAAV) mediated gene therapy is a viable approach for treating cCSNB.
- LRIT3 gene augmentation can effectively restore visual function in the mature retina.
- This strategy holds promise for treating inherited retinal diseases like cCSNB.
