Figure 3.

Histologic changes in animals receiving the highest vector dose (5 × 10¹¹ vg/eye) of AAV5-PR2.1-hCNGB3 or AAV5-PR2.1-cCNGB3 in study 3. (A) M728 left eye, AAV5-PR2.1-hCNGB3. A retinotomy lesion (thick white arrow) is characterized by focal disruption of outer and inner nuclear layers with prolapse of photoreceptor nuclei into the subretinal space of locally detached retina. The retinal pigment epithelium is intact. Abrupt transition to a zone of marked outer nuclear layer atrophy accompanied by loss of retinal pigment epithelium is apparent (row of black arrows). (B) M729 right eye, AAV5-PR2.1-cCNGB3. Perivascular aggregates of mononuclear inflammatory cells are evident around inner retinal vessels (white arrow). A few inflammatory cells within the vitreous chamber cling to the inner limiting membrane (black arrows). (C) M730 left eye, AAV5-PR2.1-hCNGB3. Inflammatory cells surrounding a choroidal vessel (white arrow) extend into the subretinal space. There is accompanying retinal detachment, atrophy of inner and outer segments, and retinal pigment epithelial attenuation. (D) Boxed region in (C) reveals an inflammatory infiltrate (lymphocytes and plasma cells, black arrows) consistent with an adaptive immune response. Hematoxylin and eosin, bars = 100 μm (A), 50 μm (B and C), and 10 μm (D).