When I’m Cleaning Windows
Kinoshita’s CEC+ROCK approach to treating corneal endothelial cell dystrophies enters the clinic
Mark Hillen |
If you view the cornea as a window, then you might consider corneal endothelial cells (CECs) as the window cleaner. A single layer that resides at the bottom of the cornea, they keep the cornea clear by transporting fluid and regulating corneal hydration. In a healthy cornea, there are about 2,000 CECs per square millimeter; in corneal dystrophies, that number starts to drop. The CECs respond by spreading out to compensate, but by the time the CEC count drops to 400 CECs/mm2, they’re overwhelmed. The cornea swells and becomes opaque.
Shigeru Kinoshita and his research group in Kyoto, Japan, are well known for developing, pre-clinically, a novel approach to increasing CEC count. They harvest CECs from a healthy donor cornea, then culture and subculture them ex vivo (1)(2)(3). The cultured cells are recovered and supplemented with a ROCK inhibitor, and then injected into the anterior chamber of the eye, having the recipient lie face down for hours to let gravity (and cell adhesion) do the work of integrating the CECs to the posterior cornea. In rabbits and monkeys, it worked well, increasing CEC levels, and restoring clarity to the cornea. Given that donor cornea tissue is in short supply, what’s nice about this approach is that one donor cornea could be used to prepare CECs for multiple recipients – it’s usually one donor, one recipient with traditional keratoplasty procedures. But the real question was: could it work in humans?
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