Two New Techniques Get Us Closer to Regenerating Eyeballs

Very different stem cell-based methods arrive at a common cause: restoring vision.

Mar 10 2016, 11:00am

Image: Africa Studio/Shutterstock

Of the body's various complicated machines and machines within machines, the complexity of eyes is among the most daunting. The tissues themselves are highly specialized, but the entire eyeball package—the intricacies and developmental processes involved—is at another level altogether. It's no wonder that blindness is so often irreversible, and so often considered a disability to adapt to and cope with rather than one to medically overcome.

Using stem cells to regenerate eye tissues is itself hardly a novel idea, and studies have shown that it's both possible and reasonable to grow certain ocular cell types from this base. One strategy involves the harvesting of stem cells from a patient and using them to regrow the epithelial cells that make up the outermost layer of the cornea in a lab, restoring vision to patients who had suffered from ocular chemical burns. The catch, however, is that the stem cells needed must be harvested from the cornea itself, and it's not always possible to grab enough of them.

The ideal method would be tricking regular old adult cells into becoming induced pluripotent stem cells (iPSCs)—cells that can essentially become anything—which would be sufficient to provide a base for growing new cells useful for therapy. Doing so requires mirroring the stages of eye development, as we again need to wind up with the right corneal cells from which we can generate the needed epithelial cells.

This is just what was accomplished by ophthalmologists at Osaka University, who describe in Nature a new technique for regrowing the corneal cells using iPSCs in a way that mirrors natural eye development.

The Osaka group, led by opthamologist and stem cell researcher Ryuhei Hayash, used iPSCs to create what they call the self-formed ectodermal autonomous multi-zone (SEAM). This a sort of eye-in-a-dish containing concentric zones that mimic in many ways the developmental process of an actual eye. In a SEAM, each of the four zones contains characteristics of some part of the ocular surface ectoderm, e.g. the class of structures that include the lens, cornea, and other obviously crucial features of the eye. Among the SEAM zones is one expressing genes characteristic of epithelial cells, which is what the researchers targeted.

In a separate Nature News and Views article, Julie T. Daniels, a professor of regenerative medicine and cellular therapy at University College London who was not involved in the Osaka research, explains that the "authors cultured transplantable sheets of corneal epithelium from the selected cells, and demonstrated that these sheets could restore a healthy corneal epithelium in rabbits in which corneal epithelial stem cells had been experimentally depleted."

In a second study in the same issue of Nature, researchers from Sun Yat-sen University in China and other institutions offer a different but similarly promising approach to eye regeneration. This one involves regeneration of the lens itself, enabled by a new surgical method of removing cataract-clouded lenses that leaves enough lens epithelial stem/progenitor cells (LECs) to regenerate new lenses. There were able to achieve functional lens regrowth in rabbits, macaques, and even human infants.

"Our method differs conceptually from current practice, as it preserves endogenous LECs and their natural environment maximally, and regenerates lenses with visual function," the Chinese group writes. "Our approach demonstrates a novel treatment strategy for cataracts and provides a new paradigm for tissue regeneration using endogenous stem cells."

So, given the fundamental difficulty in restoring eyesight from cataracts and damaged corneas, this is all pretty exciting. Blindness isn't cured, but in some cases it appears that vision can be restored using these new approaches.

"Whether either of the reported therapies will lead to cornea or lens transparency that can be maintained in the long term remains uncertain," Daniels cautions. "However, these exciting studies take us away from simple therapies that involve like-for-like replacement of single mature cell types, and open up the possibility of therapeutic manipulation of the broader stem-cell environment in the eye."