Figure 5.

Dose escalation of tetra-siRNA^Htt in porcine eyes

(A) Schematic of how porcine eyes were processed and where eyes were injected. The central part was used for histological analyses and the dorsal and ventral parts of the eye were used for quantitative analyses. ONH, optic nerve head. (B) Distribution of Cy3-labeled siRNA across the eye 14 days postintravitreal injection at doses indicated. (C) Retinal cross-section of eyes 14 days postintravitreal injection with siRNAs. Doses are indicated on the top of each column. Sections were stained for GFAP (center row) or Iba1 (bottom row) to visualize activation of gliosis and migration of microglia, respectively. Blue: nuclei marked with DAPI; green: GFAP or Iba1 as indicated; red: siRNAs marked by Cy3 label. In each panel, half of the blue signal and for rows 2 and 3 the red signal were removed to better visualize the green signal in rows 2 and 3 and the red signal in row 1. Scale bar: 100 μm. (D) Percentage quantification of remaining retinal HTT protein when compared to NTC at 14 days postintravitreal injection at doses indicated in the bar graph. Each quantification represents the average of the 4 quadrants of 1 eye. Error bars: SD; significance is compared to NTC. ∗p < 0.05; ∗∗∗p < 0.001.