Retinal degeneration causes blindness by destroying the photoreceptor cells in the retina. Some forms of degenerative blindness leave intact other cell populations, however. What if those populations could be granted some of the same mechanisms used by photoreceptor cells to pass signals to the optic nerve? Researchers here demonstrate a gene therapy that does just this, a most interesting feat of engineering. It is still a poor alternative to prevention of the condition, or restoration of lost photoreceptor cells, but it is no less impressive for it. This is truly an age of biotechnology.
Scientists inserted a gene for a green-light receptor into the eyes of blind mice and, a month later, they were navigating around obstacles as easily as mice with no vision problems. They were able to see motion, brightness changes over a thousandfold range and fine detail on an iPad sufficient to distinguish letters. The researchers say that, within as little as three years, the gene therapy - delivered via an inactivated virus - could be tried in humans who've lost sight because of retinal degeneration, ideally giving them enough vision to move around and potentially restoring their ability to read or watch video.
Correcting the genetic defect responsible for retinal degeneration is not straightforward, because there are more than 250 different genetic mutations responsible for retinitis pigmentosa alone. About 90 percent of these kill the retina's photoreceptor cells - the rods, sensitive to dim light, and the cones, for daylight color perception. But retinal degeneration typically spares other layers of retinal cells, including the bipolar and the retinal ganglion cells, which can remain healthy, though insensitive to light, for decades after people become totally blind. In their trials in mice, the team succeeded in making 90 percent of ganglion cells light sensitive.
To reverse blindness in these mice, the researchers designed a virus targeted to retinal ganglion cells and loaded it with the gene for a light-sensitive receptor, the green (medium-wavelength) cone opsin. Normally, this opsin is expressed only by cone photoreceptor cells and makes them sensitive to green-yellow light. When injected into the eye, the virus carried the gene into ganglion cells, which normally are insensitive to light, and made them light-sensitive and able to send signals to the brain that were interpreted as sight.