Looking Back, for the Future
From keratoconic to embryonic: the eye drop that promises to reinforce the cornea by inducing keratocytes to produce embryonic collagen
The 1985 film Back to the Future featured the song “Back in Time” by Huey Lewis and The News. And progressive eye diseases like keratoconus make you wish you could do exactly that: go back in time. For several years, this is exactly what Trevor Sherwin and his team at the University of Auckland have been looking to do to keratocytes, in order to stabilize the cornea in patients with keratoconus.
Curious to know how plastic keratocytes are, they asked whether keratocytes can “remember” their developmental origin – the neural crest. They do. When keratocytes were exposed to factors which stimulate neural tissue, they began to express neuronal-specific proteins (1). This led the team to ask whether they could also induce the production of type II collagen – found in the developing embryonic cornea – reasoning that “keratocytes also have a memory of producing this collagen during eye development which can be reawakened when provided with the correct stimulus.”
It appears that the correct stimulus is their eye drop, which contains a combination of a steroid and a growth factor. “So far our results [with the eye drop] have shown success in producing type II collagen which both thickens and stiffens the cornea in human tissue in vitro, and rodent corneas in vivo,” says Sherwin, adding, “This naturally led to our team proposing this as a therapeutic treatment for keratoconus.”
Their aim is to show that the eye drop is feasible for treating corneas in living people with lasting effects. Currently, their combination eye drop is being tested in sheep, to demonstrate its short-term and long-term feasibility in thickening and stiffening the cornea in a new shape. “If successful, we envisage that we would be able to treat keratoconic patients with the eye drop to thicken and stabilize the cornea at the same time as reducing excessive ‘coning’,” says Sherwin.
Data from the sheep trial is expected in early 2017, and following this, Sherwin and his team are planning to seek regulatory approval to commence clinical trials. “Because the reagents have been used independently in previous clinical trials, we do not expect a long approval process and would hope to be entering human application relatively quickly,” he says. Beyond helping keratoconic patients, Sherwin and his team’s next research goal will be to translate the technology to reshape and stabilize the corneas of myopic eyes: “Myopes already use shape forming contact lenses for transient effects – combining this approach with our treatment may prove very effective in correcting myopia.”
So sending corneal keratocytes “back in time” may form part of the future of keratoconus and myopia treatment. Watch this space.
- CA Greene et al., “Cells from the adult corneal stroma can be reprogrammed to a neuron-like cell using exogenous growth factors”, Exp Cell Res, 322, 122–132 (2014). PMID: 24370575.