Corneal Endothelial Cell Migration and Proliferation Enhanced by Rho Kinase (ROCK) Inhibitors in In Vitro and In Vivo Models.

Purpose: To explore the role of Rho-associated kinases (ROCK) in corneal physiology and regeneration, and the effects of suppressing its activity in stimulating corneal endothelial cell proliferation and migration in vitro and in vivo. Methods: Immunohistochemistry was performed to detect RhoA and ROCK-1 and ROCK-2 in human corneal tissue. Adult porcine corneal endothelial cells (CECs) were isolated, grown to confluence, and further characterized. Under the treatment of ROCK inhibitors, changes in the cellular distribution profile of ZO-1 and F-actin were examined by immunofluorescence staining. Corneal endothelial cells migration was evaluated by scratch assay and analyzed with Axiovision software. Cell proliferation was quantified using Click-iT EdU HCS Assay. In vivo, the corneal endothelia of rabbits were surgically injured and H-1152 was topically applied for 10 days. Progress of wound healing was evaluated daily by monitoring corneal edema, inflammation, and thickness using slit-lamp examination, photography, and pachymetry. Rabbits were euthanized and enucleated for further evaluation. Results: H-1152 exhibited significant stimulatory effect on CEC migration and proliferation in vitro compared with both untreated and Y-27632-treated cells. Furthermore, topical administration of H-1152 led to marked reduction in corneal edema and formation of multinucleate CECs in vivo suggestive of proliferation associated with healing. Conclusions: H-1152 exhibited a better stimulatory effect on CEC migration and proliferation in vitro than Y-27632. Our findings suggest that topical administration of H-1152 promotes healing of injured corneal endothelium in vivo. These results demonstrate the efficacy of ROCK inhibitors as a potential topical therapy for patients with corneal endothelial disease.

The changing fate of the corneal endothelium in cataract surgery.

PURPOSE OF REVIEW: Corneal endothelial cell loss remains a well known, undesirable side-effect of cataract surgery that may, in severe cases, negatively impact patients' postoperative visual outcomes. This article reviews the current literature and describes in detail how the degree of corneal endothelial cell loss is influenced by specific patient risk factors, as well as the arrival of newer surgical techniques and technologies. RECENT FINDINGS: Recent studies have demonstrated a reduction in corneal endothelial cell loss after phacoemulsification with the use of viscoelastic materials and modifications in phacoemulsification technology. Some patient characteristics may predispose patients to increased endothelial cell loss during cataract surgery. SUMMARY: Advances in surgical technique, the implementation of newer surgical technologies such as torsional ultrasound and viscoelastic devices, and aspects of patients' preexisting medical history may lead to varying degrees of endothelial cell loss after cataract surgery. Appropriately addressing these issues during the perioperative period may improve the rate of endothelial cell loss, and thus further enhance the visual outcome of patients undergoing cataract surgery.