18 June 2012

Corneal endothelium: cell therapy instead of transplantation

Japanese scientists have learned how to restore the transparency of the cornea

NanoNewsNetRegenerative medicine – the use of specially grown tissues and cells for the treatment of injuries and diseases – has proved to be quite effective in the treatment of diseases of a number of organs, including the heart, pancreas and cartilage.

However, attempts to treat pathologies of the corneal endothelium, a cellular monolayer on its inner surface, with these methods were less successful. A group of Japanese scientists has developed a method to overcome the main obstacle on this path. The results of the work are published online in The American Journal of Pathology (A ROCK Inhibitor Converts Corneal Endothelial Cells into a Phenotype Capable of Regenerating In Vivo Endothelial Tissue).

Corneal endothelial dysfunction is the main cause of severe visual impairment, since it is the endothelial cells that maintain the transparency of this eye structure. Grown and injected corneal endothelial cells (CECs) can be washed off by tissue fluids of the body, which impairs their adhesion to the surface of the cornea. Previous studies have shown that the adhesion of CECs is hindered by the signaling pathway of the enzyme Rho-associated kinase (Rho-associated kinase, ROCK). Noriko Koizumi, MD, PhD, from Doshisha University and his colleagues have found that CECs transplantation in combination with a low molecular weight compound that inhibits ROCK (Y-27632) allows for the restoration of corneal transparency.

In experiments on rabbits, scientists injected grown CECs into the anterior chamber of the eyes of animals with damaged corneal endothelium. The introduction of CECs without Y-27632 caused opacity and swelling of the cornea. Injections of CECs in combination with Y-27632 resulted in a complete restoration of its transparency within 48 hours. No complications associated with injectable cell therapy were observed, and the cells of the endothelium restored with Y-27632 had a normal hexagonal shape.


From left to right: injection of cells with an inhibitor; injection without an inhibitor; control.
(Photo: N. Okumura et al.)

Since rabbit CECs reproduce very quickly in a living organism, another series of experiments was carried out – with monkey CECs, which are closer to human ones. CECs transplantation to primates and the resulting monolayer of hexagonal cells also allowed the corneal transparency to be restored for a long time. Thus, there is every reason to believe that the cell adhesion modified by the ROCK inhibitor can become the basis for the development of an effective method for the treatment of this pathology in humans.

The existing surgical methods of replacing the damaged corneal endothelium are technically very complex. In addition, surgeons face another serious problem – a shortage of donor cornea. According to Dr. Koizumi, the strategy he developed for using cell therapy in combination with a ROCK inhibitor may eventually lead to new therapeutic methods, and not only for the treatment of corneal endothelial dysfunction, but also for a number of other pathologies.

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