Distribution of different siRNA chemistries following intravitreal delivery
(A) Schematic of modifications on the siRNA backbone and ribose. (B) Schematics of the 12 configurations used, showing in the first row the structures of different valences and in rows 2–3 the structure of the conjugates. (C) Representative images of retinal cross-sections 3 days postintravitreal injection of 3 μg of siRNA per eye. Valency or conjugate is indicated in each panel in the same order as shown in (B). Blue: nuclei marked with DAPI, red: siRNAs labeled with Cy3. In each panel, half of the blue signal was removed to better visualize the red signal. Vertical bars indicate the height of different layers. Scale bar: 50 μm. Histology was repeated with at least N = 3 retinas.