Light-sensitive proteins in chlorophyll may provide
treatment for some eye diseases.
by Carolyn Krause
Reprinted with permission from the Oak Ridge National Laboratory ORNL Reporter, Issue 30, September 2001.
Spinach, a vegetable famously rich in vitamins and minerals, can be safely assumed to be good for the eyes. A collaboration between ORNL researchers and the University of Southern California is investigating whether it might someday even restore sight to the legally blind.
In people who suffer from age-related macular degeneration or retinitis pigmentosa, the photoreceptor ability of the retina is lost even though the neural wiring from the eye to the brain remains intact. Eli Greenbaum and his colleagues in the Chemical Technology Division propose replacing these inactive photoreceptors with spinach protein, which has a similar reaction to light that may prove able to trigger optical signals to the brain.
Chlorophyll-containing proteins in spinach give off a small electrical voltage after capturing the energy of incoming photons of light. Called Photosystem I, or PSI (pronounced PS One), the main function of this photosynthetic reaction center protein is to perform photosynthesis, using the energy of the sun to make plant tissue. The same spinach protein might one day be used to replace key, light-receiving parts of the human eye that have lost their ability to function.
Eli proposed using the proteins to treat vision loss after meeting with Mark Humayun of the Doheny Retina Institute at USC. Humayun and his research team showed that if retinal tissue is stimulated electrically using pinhead-sized electrodes implanted in the eyes of legally blind patients, many of these people can perceive image patterns that mimic the effects of stimulation by light.
It might be possible, Eli suggests, to use PSI proteins to restore photoreceptor activity. ORNL experiments show that PSI proteins can capture photon energy and generate electric voltages of about one volt. The question is, can these voltages trigger neural events, allowing the brain to interpret images?
Degeneration of the retina (the light-sensitive layer of tissue at the back of the eye) has left 20,000 people totally blind in the United States, and another half-million visually impaired. One condition, retinitis pigmentosa, or RP, is an inherited condition in which the rods (specific photoreceptor cells in the retina) degenerate. Eventually, the disease diminishes a person’s ability to see in dim light and gradually can reduce peripheral vision. Another disease, age-related macular degeneration, or AMD, affects the macula, or center of the retina. People rarely go blind from AMD but may have great difficulty reading, driving, and performing other activities. When light is focused onto the macula, millions of cells change the light into an electrical current that tells the brain, by way of the neural wiring, what the eye is seeing.
Eli and his colleages want to try to implant the light-sensitive proteins in damaged retina to see if they can generate electrical impulses that might result in sight. Using Laboratory-Directed Research and Development funds, Eli, Tanya Kuritz and James W. Lee, all of Chem Tech, and Frank W. Larimer of the Life Sciences Division are working with Ida Lee and Barry D. Bruce, both of the University of Tennessee, and Humayun and his team at the Doheny Retina Institute at USC.
“We have assembled an outstanding interdisciplinary team of scientists, vitreo-retinal surgeons, ophthalmologists and biomedical engineers, to attack this important problem,” Eli says. The project is based on recent original discoveries in the Chem Tech Division.
“Using Kelvin force microscopy, we have performed the first measurements of voltages induced by photons of light from single photosynthetic reaction centers,” Eli says.” The measured photovoltage values, typically one volt or more, are sufficiently large to trigger a neural response.” The work was published last year in an issue of the Journal of Physical Chemistry B.
“We are proposing the insertion of purified PSI reaction centers into retinal cells to determine whether they will restore photoreceptor function in persons who have AMD or RP. Once we demonstrate this is possible, USC researchers will test the technique in the laboratory and, if feasible, later in humans in clinical trials.”
In recent research, the collaborators showed that PSI reaction centers could be incorporated into a liposome, an artificial membrane that mimics the composition of a membrane of a living cell. They also showed that the PSI can be functional inside a liposome–that is, it produces the experimental equivalent of a voltage when light is shone on it. A liposome will likely be used to deliver PSI to a retinal cell.
Eli has long believed that his group’s research in photosynthesis could have important impacts on humans in terms of energy production and biomolecular electronics. Now, he is especially excited that it also could lead to restoration of vision to the blind.