Retinitis pigmentosa (RP) is an incurable genetic disease caused by the loss of light-sensing cells called photoreceptors. When light hits the retina, a specialized tissue in the back of the eye, light-sensitive cells called photoreceptors transform the light signal into electrical impulses. Through a series of connections, these signals are transmitted back to the brain where additional processing results in the experience of sight.
In patients with retinitis pigmentosa, the initial step in this process is critically impaired. The photoreceptors degenerate, losing their ability to transform light into visual signals. Initially, RP patients develop night blindness; this proceeds to tunnel vision and eventually total blindness.
“Most people with RP are legally blind by age 40, with a central visual field of less than 20 degrees in diameter.”
Photoreceptors allow us to see in both daylight and nighttime, and are comprised of two types of cells: rods and cones. Rods are sensitive to dim light, and are located away from the center of the retina. Because of rods’ sensitivity to dim light, their degeneration primarily impacts peripheral and night vision. Cones, on the other hand, are responsible for color and sharp central vision. These cells are concentrated toward the center of the retina. When cones begin to degenerate, they can no longer process daylight and high acuity vision, such as that required for reading, driving and recognizing faces. In RP, sometimes the rods degenerate first; other times, the cones. Night blindness, caused by rod degeneration, is one of the earliest and most frequent symptoms of RP. In other types of visual loss, people experience cone degeneration first, leading to decreased central vision and color blindness.
Initially, RP patients develop night blindness; this proceeds to tunnel vision and eventually total blindness.
Retinitis pigmentosa is a rare condition, directly affecting one in every 4,000 people. Accordingly, RP is classified as an “orphan” disease by the Food & Drug Administration. RP often runs in families; however, it can also occur spontaneously, as a result of recessive or novel genetic mutations. Mutations in more than 60 different genes have been shown to lead to RP. These mutated genes are ones that characteristically play important roles in the development and functionality of photoreceptors. These mutations often lead to a loss or dysfunction of important proteins, causing cells to stop functioning properly and ultimately die.
RP is typically diagnosed in adolescents and young adults. In all cases, RP is a progressive disorder (meaning it worsens over time), however, the rate of progression and degree of visual loss varies from person to person. Most people with RP are legally blind by age 40, with a central visual field of less than 20 degrees in diameter. There is currently no cure or established treatment for RP.
Progress Towards A Cure
Loss of sight is a traumatic event that dramatically affects one’s quality of life, making it nearly impossible for afflicted individuals to perform daily tasks independently or engage with the world around them. These patients need better therapies that utilize the tools of tomorrow. With more than $17 million in funding from Proposition 71 and the California Institute for Regenerative Medicine (CIRM), California researchers are seeking to do exactly that. These scientists are using stem cells to rescue the receptors from further damage, and, hopefully, replace the damaged or lost photoreceptor cells with new ones.
Loss of sight is a traumatic event that dramatically affects one’s quality of life, making it nearly impossible for afflicted individuals to perform daily tasks independently or engage with the world around them.
A team of scientists at UC Irvine, led by Dr. Henry Klassen, are using specialized stem cells called retinal progenitor cells, which can be transplanted into the eye. The benefit of transplanting these cells is two-fold: First, they offer support to the sick and dying photoreceptors and second, they can eventually develop into photoreceptors themselves. By restoring the health of light-sensing cells in the retina, this stem cell therapy attempts to preserve and enhance the ability of these patients to see. Retinitis pigmentosa represents a “proving ground” disease for stem cell therapy for a number of reasons:
- Apart from photoreceptor destruction, the rest of the visual system is intact and functional;
- The degeneration of photoreceptors in RP is similar to the degeneration of other types of cells in the brain and nervous system, so can serve as a model for more common types of neurodegeneration;
- Previous research has already demonstrated this transplantation technique in animals with photoreceptor degeneration; thus, the scientific feasibility of treating RP in this way has already been established in principle.
This approach is currently being tested in a “first-in-kind” human clinical trial by implantation of retinal progenitor cells to treat retinitis pigmentosa. This Phase I/IIa trial is designed to evaluate the safety of this therapy. To date, twenty-eight participants with RP—all visually disabled due to the degenerative disease—have received cell injections, either at the Gavin Herbert Eye Institute in Irvine or at Retina Vitreous Associates in Los Angeles. The first phase of the trial is now complete, and to date the treatment has been well-tolerated. This effort is in conjunction with the California Institute for Regenerative Medicine’s new Alpha Stem Cell Clinic network, which is designed to accelerate the timeframe of clinical trials, getting safe and effective therapies to patients as quickly as possible.
The initiation of this clinical trial represents the culmination of a research project stretching back more than a decade. According to Dr. Klassen, this project was significantly accelerated by support from California’s stem cell agency.