United States-based researchers have restored light sensitivity in animal subjects with a condition similar to retinitis pigmentosa. Their work has demonstrated that it is possible to create replacement genetically modified [i.e., via gene therapy] light-sensing retinal cells from cells that do not normally react to light.
This research is in its earliest stages and has been conducted only with laboratory animals; nevertheless, the concept shows great promise for persons with retinitis pigmentosa and some forms of Leber congenital amaurosis.
The research, entitled Restoration of visual function by expression of a light-gated mammalian ion channel in retinal ganglion cells or ON-bipolar cells (explained below) was published in the December 8, 2014 Early Edition of Proceedings of the National Academy of Sciences. Proceedings, first published in 1915, is the official journal of the National Academy of Sciences of the United States. It publishes research reports, commentaries, and reviews that span the biological, physical, and social sciences.
The authors are Benjamin M. Gaub, Michael H. Berry, Amy E. Holt, Andreas Reiner, Michael A. Kienzler, Natalia Dolgova, Sergei Nikonov, Gustavo D. Aguirre, William A. Beltran, John G. Flannery, and Ehud Y. Isacoff, who represent the following institutions: University of California, Berkeley; School of Veterinary Medicine and Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Lawrence Berkeley National Laboratory, Berkeley, CA.
About Retinitis Pigmentosa
Retinitis pigmentosa (RP) is part of a large group of hereditary retinal conditions or dystrophies, involving one or several layers of the retina. RP occurs in approximately 1 in 4,000 people in the United States. At present, there is no cure.
Most individuals with RP initially experience difficulty with night vision and in low light levels. Central (straight ahead) vision is usually retained until late in the course of the disease, while peripheral (or side) vision becomes progressively more constricted, resulting in “tunnel vision” (pictured above).
Primarily, the retinal rod cells – light-sensitive, specialized retinal receptor cells that activate at low light levels and provide night vision – are involved, but there may also be some involvement of the retinal cone cells, which function best in relatively bright light and provide color vision and greater visual acuity than do rod cells.
You can read more about retinitis pigmentosa research at What Is Retinitis Pigmentosa? by Frank J. Weinstock, MD, FACS at the VisionAware website.
About the Research
Excerpted from Gene therapy could help with inherited blindness: Researchers managed to create new light-sensitive cells, via the UK National Health Service (NHS) News:
Experiments on blind mice and dogs have found that cells in the retina which are not normally light-sensing (i.e., retinal ganglion cells) can be genetically modified to respond to light.
[Editor’s note: Ganglion cells, also called retinal ganglion cells, are neurons, or nervous system cells. They are located near the inner surface of the retina and give rise to optic nerve fibers that transmit information from the retina to several regions in the brain.]
The researchers used gene therapy to modify these cells. The cells responded to light after they were activated with an injection of a chemical called MAG, with the effects lasting up to nine days.
This animal study tested whether cells in the retina that do not respond to light could be made to respond. The [researchers] used genetic modification to produce a light receptor protein and a light-sensing chemical compound. This two-step process was tested on the retinas of blind mice and dogs.
Previous research found that although there is loss of these photoreceptors on the outer level of the retina, the connecting nerves underneath still function. Researchers were interested in whether they could get these connecting nerves (the retinal ganglion cells) to act as light-sensing cells, which could restore some vision.
The researchers first used genetic engineering to insert a gene for a receptor that responds to light in the presence of a chemical called maleimide-azobenzene-glutamate (MAG). This process uses a modified virus, called adenovirus, to carry the gene into cells. The genetically modified virus is injected into the retina. The scientists were able to get retinal ganglion cells to produce this receptor.
Afterwards, an injection of MAG could turn on the light receptors when they are exposed to light. However, the first set of laboratory experiments did not work well because the level of light required to activate the new light receptors was so high that it damaged the retina. After modifications, they produced a slightly altered chemical compound called MAG460, which responded to a less damaging wavelength of light.
Mice genetically engineered to lose the function of rods and cones by the age of 90 days were used. The researchers injected the mice’s retinas with the adenovirus containing the light receptor gene. Afterwards, they injected the retinas with MAG460 and then measured the ability of the retinal cells to respond to light in the laboratory.
Finally, the researchers injected a canine version of the adenovirus and light receptor mixture and MAG460 into the retinas of three blind dogs and one normal dog.
The light receptors were successfully produced by most of the retinal ganglion cells. The chemical compound MAG460 they developed was able to cause the cells to react to blue or white light without causing retinal damage. The light receptor was also able to “switch off” in darkness. These experiments [illustrate] that, despite the original photoreceptors being damaged or dying, some function can be restored if other cells are undamaged.
More about the Research from Proceedings
From the article abstract:
Most inherited forms of blindness are caused by mutations that lead to photoreceptor cell death but spare second- and third-order retinal neurons.
We restored visual function to animal models of human blindness using a chemical compound that photosensitizes a mammalian ion channel. Virus-mediated expression of this light sensor in surviving retinal cells of blind mice restored light responses in vitro, reanimated innate light avoidance, and enabled learned visually guided behavior. The treatment also restored light responses to the retina of blind dogs.
Patients that might benefit from this treatment would need to have intact ganglion cell and nerve fiber layers. In general, these are patients diagnosed with retinitis pigmentosa and some forms of Leber congenital amaurosis.
Patients diagnosed with other types of blindness, for example, age-related macular degeneration or diabetic retinopathy, would not be candidates for this treatment.