An Eye for an Eye?

Curing blindness has often held a certain fascination for humankind. Mythological and religious lore contain fantastic accounts of wizards, prophets, gods, and demigods who have the ability to restore sight to those suffering from blindness. But this kind of power may not be so improbable anymore. Recent news shows that scientists are one step closer to finding a solution and accomplishing the see-mingly impossible.

On July 8, Rama et al., Italian researchers based at the San Raffaele Scientific Institute and the University of Modena, reported that transplantation of stem cells was successful in renewing and repairing corneal epithelium.¹ Knowing what we do about skin grafts and other forms of regenerating tissue, this experiment may not seem so impressive. However, this stem cell treatment affected not only structural restoration but also functional repair: patients who underwent the therapy had their sight significantly restored. The experiments reversed many degrees of blindness in the participating individuals, most of whom suffered from ocular burns.

Damage to the cornea is said to be the cause of 1.5 million cases of vision loss every year,² so developing a scientific procedure to repair the cornea would be a considerable advance in improving quality of life for many individuals. An intact and clear cornea is essential to vision because it acts as the eye's outermost lens. The cornea focuses incoming light onto the retina, the region of the eye that contains rod and cone cells-photoreceptors sensitive to contrast and color.

For individuals with retinal disorders stemming from congenital blindness, or blindness caused by a faulty gene, certain tactics have shown potential for repair. In the case of Leber's congenital amaurosis, photoreceptors cannot function because a mutant gene fails to produce the protein necessary to absorb light. Gene therapy, or the process of delivering a functional gene to rods or cones via viruses, has significantly restored both day and night vision in patients in a long-term, persistent manner.^3,4

But if the cornea is injured, the body can usually respond itself with stem cells generated from the limbus. An area between the cornea and the bulbar conjunctiva, the limbus produces progenitors that mediate epithelial repair. However, victims of ocular burns caused by chemical, thermal, or UV exposure suffer from destroyed limbi and therefore lose their intrinsic capacity for regeneration. A deficiency of limbal stem cells disrupts normal corneal repair, such that undirected growth in the cornea causes scarring and, consequently, debilitating vision loss.

Prior research has elucidated that human limbal stem cells can be identified and thus isolated both in vivo and in vitro by expression of a transcription factor, p63. Additionally, cultures of these stem cells contain holoclones, cells that have tremendous growth capacity compared to other clonal types and are thus therapeutically relevant. Therefore, as long as patients have some spared limbus region, even individuals with severe bilateral limbal stem cell deficiency should benefit from transplantation therapy. Researchers have utilized this information in an effort to restore corneal epithelia, and with amazing results.

Last year, for instance, researchers in Australia reported a novel, inexpensive contact lens-based technique for regenerating corneal epithelial cells in damaged eyes.⁵ They biopsied limbal or conjunctiva progenitor cells from three patients' healthy eyes. Instead of directly transplanting the stem cells, Girolamo et al. plated the cells onto contact lenses for their patients to wear. They saw significant restoration of the cornea and vision, to the point where two of the three went from being legally blind to reading part of an eye chart and the third was even able to pass a driving exam. Thus, targeting the limbus is admittedly not a wholly unique approach. But Rama et al.'s newly reported and still extremely promising findings involve 112 patients, which is a significantly larger subject population than prior studies like those conducted in Australia.

Hypothesizing that they could transplant intact limbal stem cells into eyes suffering from ocular burns, Rama et al. biopsied patients' limbi, cultured the progenitor cells, and grafted the cultures back into patients' damaged eyes. They then followed the outcome of the treatments for an entire decade. The transplantation procedure was successful for 75% of the patients treated over that time period, demonstrating not only the power of stem cell therapy, but also the remarkable regenerative capacity of the human body.

Image Credit: http://wikimedia.org

1. Rama, P. et al. Limbal Stem-Cell Therapy and Long-Term Corneal Regeneration. New England Journal of Medicine 363, 147–155 (2010).
2. Smith, D. "Stem-Cell-Coated Contact Lenses Are Curing the Blind." Popular Science. June 3, 2009.
3. Blue, L. "A Gene to Cure Blindness." Time. May 18, 2007.
4. Cideciyan, A. V. et al. Vision 1 Year after Gene Therapy for Leber's Congenital Amaurosis. New England Journal of Medicine 361, 727–727 (2009).
5. Di Girolamo, N. et al. A contact lens-based technique for expansion and transplantation of autologous epithelial progenitors for ocular surface reconstruction. Transplantation 87, 1571–1578 (2009).