Figure 5.

ANGPTL7 antibodies caused a increase in outflow facility and decrease in IOP. (A) Human donor eyes were placed on our custom eye mounts in a humidified and temperature-controlled water bath. Aqueous humor was extracted, and eyes were perfused. Effluent was collected over time. Three pairs of human donor eyes were perfused over 4 hours at a constant flow rate of 2.5 µL/min while pressure was continuously monitored to calculate outflow facility. Effluent was collected hourly. ANGPTL7 levels were dramatically higher in the effluent (445.6 ± 232.0 ng/mL; n = 18) than the aqueous humor (63.5 ± 29.2 ng/mL; n = 6; P = 0.0007, unpaired t-test). The three patients are indicated in different colors. No significant changes were seen across time points. (B) Outflow facility, reported as isotype IgG versus anti-ANGPTL7 IgG (AAb-4), in human eyes (n = 6 pairs) perfused with anti-ANGPTL7 IgG at a constant pressure of 15 mmHg showed a 61% increase in facility at 2 hours (0.24 ± 0.10 vs. 0.39 ± 0.15 µL/min/mmHg, **P = 0.0011) and a 58% increase at 3 hours (0.24 ± 0.10 vs. 0.39 ± 0.12 µL/min/mmHg, ***P < 0.0001), with 1 hour trending toward an increase in facility (0.23 ± 0. 06 vs. 0.43 ± 0 .22 µL/min/mmHg, an 88% increase; P = 0.058). Statistical significance was determined by paired t-test. (C) New Zealand White rabbits were intravitreally injected with 2 mg of an antibody targeting ANGPTL7 (AAb-1) or a vehicle control in the OD eye, and IOP was measured over 21 days. Percent reduction in IOP was calculated compared to the contralateral non-injected OS eye (n = 3 eyes at each time point, except for n = 2 on day 21 for AAb-1 after one rabbit was removed on day 18 out of an abundance of caution due to slight squinting of the OD eye). Data are shown as mean ± SD.