Table 4.
ERG responses and retinal findings in study 3 after subretinal injection of AAV5-PR2.1-hCNGB3 or AAV5-PR2.1-cCNGB3 in CNGB3-mutant dogs
| Group | Animal ID | Eye | Vector dose (vg/eye) | Cone ERG (μV) | Clinical ophthalmic examination | Histopathologic findings in retina |
|---|---|---|---|---|---|---|
| 1 | M731 | OD | 5 × 1010 | 3.94 | Retinal thinning | Variably severe retinal atrophy and loss of retinal pigment epithelium (70% of the superior retina) |
| OS | 5 × 1010 | 1.54 | Normala | Retinotomy site | ||
| M732 | OD | 5 × 1010 | 7.66 | Normala | No significant lesions | |
| OS | 5 × 1010 | 3.80 | Normala | No significant lesions | ||
| M733 | OD | 5 × 1010 | 3.17 | Normala | No significant lesions | |
| OS | 5 × 1010 | 1.57 | Normala | No significant lesions | ||
| 2 | M728 | OD | 5 × 1011 | 3.80 | Multifocal chorioretinitis and retinal thinning | Locally extensive retinal atrophy (superior retina); scattered foci of perivascular lymphoplasmacytic chorioretinitis |
| OS | 5 × 1011 | 3.16 | Retinal thinning | Locally extensive retinal atrophy (superior retina); adjacent to retinotomy site | ||
| M729 | OD | 5 × 1011 | 6.80 | Normala | Variably severe predominantly perivascular mononuclear retinitis (superior retina) | |
| OS | 5 × 1011 | 1.01 | Normala | Variably severe predominantly perivascular mononuclear retinitis (superior retina); gliotic retinotomy site | ||
| M730 | OD | 5 × 1011 | 4.42 | Multifocal chorioretinitis | Variably severe mononuclear retinitis, parenchymal and perivascular, involving most of the superior retina, and extending into the choroid with areas of RPE loss | |
| OS | 5 × 1011 | 5.22 | Normala | Several perivascular inflammatory nodules, single region of choroidal inflammation, and a focus of outer nuclear atrophy and RPE loss |
Each animal received a 0.1 mL subretinal injection of AAV5-PR2.1-hCNGB3 in the left eye (OS) and AAV5-PR2.1-cCNGB3 in the right eye (OD). The vector concentration was 5 × 1012 vg/mL in group 1 and 5 × 1011 vg/mL in group 2. Cone ERG values are the 30 Hz flicker amplitude at week 12. In animal M728, a total of 200 μL was injected in the left eye, mostly intravitreal, with only a small subretinal bleb, and there was delayed absorption of subretinal fluid in the right eye. In animal M731, there was delayed absorption of subretinal fluid in the right eye.
No visible lesions except for retinotomy scar, which was seen in all eyes.