Regenerative effects of RKI-1447 on human corneal endothelial cells: a comparative study.

BACKGROUND

To evaluate and compare the effects of two Rho-associated protein kinase (ROCK) inhibitors (Y-27632 and RKI-1447) on human corneal endothelial cell (HCEC) proliferation and wound healing.

METHODS

Using a commercial primary HCEC line, three groups of HCECs were created; control (no treatment), Y-27,632-treated, and RKI-1447-treated. The control, Y-27,632, and RKI-1447 groups were compared regarding cell proliferation (5-bromo-2-deoxyuridine [BrdU] incorporation), wound healing (ImageJ analysis), and ROCK activity (enzyme-linked immunosorbent assay [ELISA]).

RESULTS

Both RKI-1447 (1 µM) and Y-27,632 (10 µM) significantly enhanced HCEC proliferation when compared to the control group (p < 0.05). However, RKI-1447 showed a more potent effect than Y-27,632 in terms of stimulating cell proliferation under the experimental conditions tested (p < 0.05). Furthermore, endothelial wound healing was faster in the RKI-1447 group compared to the control and Y-27,632 groups (p < 0.05). Y-27,632 was found to stimulate wound healing more than the control group only in the first 24 h (p < 0.05).

CONCLUSION

This pilot study demonstrated that RKI-1447 was more potent than Y-27,632 regarding HCEC proliferation, endothelial wound healing and suppressing ROCK activity. However, further in vitro and in vivo preclinical studies are required to validate the efficacy and ocular safety profile of RKI-1447 before any consideration of clinical translation.