Research Highlights

Nature Reports Stem Cells
Published online: 9 October 2008 | doi:10.1038/stemcells.2008.133

Corneal stem cells, no exceptions

Monya Baker¹

Stem cells spread throughout the corneal surface repair general wear and tear

Layers of scaly, flat cells cover the skin. These expanses of squamous epithelium are thought to be renewed by scattered groups of stem cells, each of which is responsible for maintaining a particular region of the skin. Though it is also covered by squamous epithelium, the cornea — the clear shield covering the front of the eye — has long been considered an exception to this renewal rule. Maintenance within the cornea supposedly relies on a population of stem cells residing in the limbus, an area at the edge of the eyeball from which new cells constantly migrate to replace dying cells. Using transplantation studies, Yann Barrandon and colleagues from Ecole Polytechnique Fédérale de Lausanne in Switzerland now show that cornea epithelium actually maintains itself via corneal stem cells scattered over the ocular surface, similar to the process that occurs epithelium elsewhere in the body¹ (See Fig. 1).

Figure 1: Stem cells reside throughout the cornea

Stem cells migrating out from the limbus have been considered essential for maintaining the cornea (left). New work indicates this maintenance is sustained through stem cells scattered over the corneal surface (right).

Yann Barrandon lab, modified by Jessica Kolman

Full figure and legend (46 KB)

At first, the researchers wanted to watch cell migration across the eye, so they took limbal cells from mice that had been genetically engineered to generate a blue stain and transplanted them into mice whose cells could not make the stain. They waited as long as 11 months, but they never saw any blue stain in the cornea of the recipient mice, indicating that the transplanted cells were not migrating. The situation changed, however, if the cornea was badly injured. In this case, the transplanted cells did move into the cornea. This means that the limbus is important for wound healing and that, under normal conditions, cells resident within the cornea are sufficient to maintain it.

To explore further, the researchers conducted experiments in which they transplanted blue-staining cells from one mouse's cornea into limbal regions of another mouse and then injured the recipient's cornea. The transplanted cells then helped repair recipients' corneas. Indeed, these cells could be transplanted multiple times and were able to repair wounds within both the cornea and even produce more specialized cells found in the conjunctiva, which covers the hard, white part of the eye. Thus, not only does the cornea contain stem cells, but also these cells are capable of taking on a variety of fates depending on the environment in which they are placed. Finally, the researchers isolated and cultured cells from the conjunctiva and cornea of pigs and showed that these cells both have similar morphology and genetic signatures. Proliferating, colony-forming cells could also be obtained from samples taken from various parts of the cornea of other mammals, including, to a lesser extent, humans.

This work indicates that the cornea has more regenerating power than originally thought and also explains why various sorts of stem cells have been able to repair corneal defects.

But questions remain, says Julie Daniels of the Institute of Opthamology at University College London. "The elegant studies performed in the mouse may not be truly representatative of the mature human cornea." The assays were performed on donors who were only up to four years old. Because scientists are unsure of when corneal stem cells reach their final position of residence, she says, the assays will need to be repeated on adult corneas.