Leading researcher, Noriko Koizumi, MD, PhD, from the Doshisha University's Department of Biomedical Engineering, Faculty of Life and Medical Sciences in Kyotanabe, Japan explained:
"Corneal endothelial dysfunction is a major cause of severe visual impairment, since the cells maintain the transparency of the cornea. Injected cultured CECs can be washed off by aqueous humor flow, resulting in poor adhesion of the cells injected onto the corneal tissue.
Previous studies demonstrated that Rho-associated kinase (ROCK) signaling interferes with adhesion. We found that transplanting cultivated CECs in combination with a low-molecular weight compound that inhibits ROCK (ROCK inhibitor Y-27632), successfully achieved the recovery of corneal transparency."
The researchers cultivated rabbit CECs in the lab, which they subsequently injected into the anterior chamber of these eyes of rabbits with damaged corneal endothelia. Judging by the recovery of the corneal endothelial function, they discovered that the rabbits' corneas regained complete transparency 48 hours after they were injected with the cultivated cells and Y-27632, whilst the rabbits injected with CECs but without Y-27632 had hazy and severely swollen corneas.
The team reported no procedure-related complications, noting that the rabbits in the CEC plus Y-27632 group's reconstructed corneal endothelium regained a normal hexagonal cell shape.
The scientists decided to continue their experiments with monkey CECs, as these are more similar to human cells, but also because rabbit CECs are highly prolific in vivo.
They observed that CECs transplants in monkeys also managed to achieve a recovery of long-term corneal transparency with a monolayer of hexagonal cells, which indicates that cell adhesion modified with the ROCK inhibitor Y-27632 could potentially become an effective treatment for human corneal endothelial disorders.
The investigators note that the procedure of these developed surgical methods for the replacement of injured corneal endotheliums is technically difficult, and that treatments remain challenging due to the shortage of donor corneas. Dr. Koizumi concludes:
"The novel strategy of using a cell-based therapy combined with a ROCK inhibitor may ultimately provide clinicians with a new therapeutic modality in regenerative medicine, not only for treatment of corneal endothelial dysfunctions, but also for a variety of pathological diseases."
Written By Petra Rattue