Figure 6.

Comparative Efficacy of Two RPGR Gene Constructs at Preserving ONL Thickness

(A and B) ONL thickness topography in individual eyes injected at 5 to 6 weeks of age with 70 μL of a AAV2/5-GRK1-viral vector (titer: 7.2 × 10¹¹ vg/mL) carrying either hRPGRstb (A) or hRPGRco (B) gene constructs compared with uninjected control eyes. Treatment boundaries are based on fundus photographs of the bleb taken at the time of the injection (dotted lines), and, if visible, demarcations apparent on infrared imaging at the time of scanning (dashed lines). All eyes shown with optic nerve and major blood vessels (black), tapetum boundary (yellow), and fovea-like region (white ellipse) overlaid for ease of comparison. N, nasal retina. Z522-OD and similar labels designate the individual animal and eye. (C) Schematic describing the two methods of analysis performed to compare the efficacy of the two gene constructs. Analysis 1 uses an intra-retinal control and compares the paired loci across the treatment boundary in each eye. Analysis 2 uses the contralateral control eye and compares the loci within the treatment boundary (dashed outline) with loci at corresponding locations in uninjected contralateral eye. UnTx (red squares), untreated; Tx (green squares), treated with vector. (D) Treatment effect (difference in ONL thickness between treated and untreated retina in log₁₀ units), quantified at ∼12 weeks after treatment using intra retinal (left) and contralateral (right) control to evaluate efficacy of hRPGRstb and hRPGRco gene constructs. Symbol with error bars represents mean (± SD) treatment effect for an individual eye in each group of RPGR mutant dogs. N.S., not significant, t test.