Many people would argue that sight is the human’s most important sense as it allows us to navigate through our surroundings with ease. Dealing with loss of vision can be extremely difficult, not to mention many of the diseases that cause blindness remain to be incurable. Scientists are now looking at stem cell technology to explore new approaches to treating various types of blindness.
About The Limbal Stem Cells
Blinking and exposure to the outside world constantly damage the cells that make up the cornea (the window part of the eye). The limbal cells, a small number of stem cells at the edge of the cornea, help repair this damage. They are in charge of producing new corneal cells to replace the damaged ones. If the limbal cells are lost due to disease or injury, the cornea become permanently impaired. This disrupts the way light enters the eye, leading to a significant loss of vision.
After years of painstaking research, scientists have now developed a technique to collect limbal stem cells from a healthy donor eye or from a spared limbal area in bilateral lesions, expand the numbers in the laboratory, and transplant them into the damaged eye. Clinical trials have shown that this procedure can repair the cornea and permanently restore eyesight.
Repairing The Cornea
So far, transplantation of limbal cells to repair the cornea is the only stem-cell based therapy proven by clinical trials. Following approval by the European Medicines Agency, the European Commission gave the go signal for the sale of an advanced therapy medical product (ATMP) containing limbal stem cells to healthcare providers. This is the last step in the clinical translation process occurring after successful clinical trials.
The treatment, called Holoclar®, is the product of more than two decades of excellence in research, led by a team of world-renowned experts in the field of epithelial stem cell biology. An Italian University spin-out company named Holostem Terapie Avanzate S.r.l tested Holoclar in Good Manufacturing Practice-certified facilities in line with European legislation, and it is now being commercialized by Chiesi Farmaceutici S.p.a.
In case the corneas of both eyes are severely worn-out (bilateral limbal deficiency), the therapy will not work because there is no residual limbal cells to collect and culture. For this reason, researchers are trying to devise a different approach in which they will use oral mucosa, induced pluripotent, or embryonic stem cells to make new limbal stem cells in the lab. In theory, this solution may provide an endless source of limbal stem cells and remove the need for complex surgery for collecting them.
Replacing The Retinal Pigment Epithelial Cells
The retinal pigment epithelium (RPE) plays an important role in maintaining the retina. It regulates the transport of nutrients and waste products to and from the retina, acts as a barrier from high-energy light, and helps regenerate the worn-out tips of photoreceptor outer segments.
If the retinal pigment epithelial cells stop working due to disease or injury, then certain parts of the retina die. This leads to the onset of blindness. The most common causes of RPE cell damage are Leber’s congenital aneurosis, retinitis pigmentosa, and age-related macular degeneration.
Replacing the damaged RPE cells with transplanted healthy cells would be one way to treat these diseases. However, it is impossible to take healthy RPE cells from donors, which necessitates the need for a different source. Researchers have already produced new RPE cells from both iPS cells and embryonic stem cells in the lab. They have tested the safety of embryonic stem cell-derived RPE cells for patients with Stargardt’s macular dystrophy and AMD during the phase I/II clinical trials.
The findings of the trial, reported in 2014, ensured its safety and demonstrated engraftment of the transplanted RPE cells. While several patients have reported an improvement in vision, others experienced adverse side effects from the immunosuppression and the transplantation itself. This treatment is still not at the endpoint of its trial.
In the United Kingdom, a second Phase I/II trial exploring the use of RPEs made from human embryonic stem cells for patients with wet AMD is currently underway. For the first time ever, in September 2015, a patient underwent this procedure. The treatment is still ongoing at the Moorfields Eye Hospital under the supervision of Professor Pete Coffey as part of the London Project to Cure Blindness.
There is another clinical trial in Japan led by Japanese researcher Dr. Masayo Takahashi which transplants RPE cells derived from iPS cells into people with wet AMD. Due to concerns about mutations and regulatory changes in Japan, the trial was put on hold for several months. It has since recommenced in June 2016 and many await the findings.
Replacing Retinal Cells
In many situations where the sight becomes impaired, the problem typically lies with malfunctioning retinal circuitry. Eye disorders normally start when certain specialized cells in the circuit either die off or stop working. Having a source of new retinal cells may just be the solution for repairing the worn-out cells and help bring back vision. Despite the retina being more complicated than other components of the eye, this approach may be able to patch up the damage and even restore the optic nerve.
Once again, researchers turn to stem cell technology to generate a source of replacement cells. Several studies now prove that retinal cells can be derived from both iPS and embryonic stem cells. Unlike cell transplantation, the direct treatment of the retina may allow patients to restore their lost vision to some degree. There are currently no clinical trials planned for this approach as significant research is still required.
Stem cell technology holds promising outcomes for patients who suffer from visual disorders. Central to the studies being conducted to create new therapies is learning of how various types of stem cells behave and finding effective ways to harness their curative potential. It’s still not a one-stop, generic cure, but it does hold exciting possibilities for the production of components that we can use to repair the eyes.