The Effect of AMA0428, a Novel and Potent ROCK Inhibitor, in a Model of Neovascular Age-Related Macular Degeneration

Abstract

The results suggest that targeting ROCK with AMA0428 not only reduces neoangiogenesis, but also blocks inflammation and fibrosis (contrary to VEGF suppression). These results point to a potential therapeutic benefit of ROCK inhibition in neovascular AMD.

Modulation of wound healing in glaucoma surgery

“…Also in a rat model of Crohn's disease, oral administration of the ROCK inhibitor Y-27632 significantly reduced colonic inflammation (Segain et al, 2003). The anti-inflammatory, antiangiogenic, and antifibrotic effects ROCK inhibitors are also confirmed in other animal models for ocular pathologies such as corneal wound healing (Sijnave et al, 2015) and age-related macular degeneration (Hollanders et al, 2015). Taken together, the Rho-ROCK pathway is involved in different processes of importance in the wound healing cascade and as such, inhibition of ROCK might be a promising strategy to modulate the healing response after glaucoma surgery.…”

Topical Ripasudil Suppresses Retinal Ganglion Cell Death in a Mouse Model of Normal Tension Glaucoma

“…19 The Rho/ ROCK pathway is involved in various neuropathological conditions, such as spinal cord injury, 20 Alzheimer's disease, 21 and demyelinating disease, 22,23 and ophthalmologic diseases, such as glaucoma, 24 corneal endothelial dysfunction, 25 diabetic retinopathy, 26 and age-related macular degeneration. 27 ROCK signaling has therefore attracted interest as a potential therapeutic target for these diseases.…”

ROCK inhibitors in ocular disease

“…Fourteen days after CNV induction, repeated intravitreal injections of AMA0428 (100 or 1000ng on days 0, 4, 10) had a remarkable inhibitory effect on angiogenesis and vessel leakage similar to anti-VEGF (DC101) treatment. Moreover, one month after the laser injury, multiple intravitreal administrations of this ROCK inhibitor (100 or 1000 ng, on days 0, 4, 10, 20) significantly reduced fibrosis in the mouse CNV model whereas the VEGF-receptor 2 inhibitor (DC101) had no effect [16].…”

“…This soft drug was in phase II clinical trials in 2014, however results from the trials have not yet been disclosed. Another soft ROCK inhibitor, AMA0428, has been shown to not only reduce neoangiogenesis but also to block inflammation and fibrosis in an animal model of neovascular age-related macular degeneration (AMD) [16].…”