In the May 21, 2007 online issue of Nature Medicine, researchers report on animal experiments that used gene therapy to prevent the death of cone photoreceptor cells in the retina, thus restoring vision to blind mice.

Though they are vastly outnumbered by the light-sensitive rods in the retina, the color-sensitive cones are what ultimately determines whether someone can see, at least during daylight conditions. Rods, which are what lets us see under conditions of low light, are so light-sensitive that they become completely saturated in daylight.

The transduction of light into neural responses is the first step in vision. In their paper, the researchers used adeno-associated virus to deliver a gene that codes for a critical protein in the transduction process to mice with a mutation that leaves them unable to transduce light into a neural response in their cones. The mice are a model for achromatopsia, an inherited disorder that is characterized by poor visual acuity and an inability to see color.

The gene therapy effectively targeted two of the three types of cones: red and green cones. The third type, blue cones, make up less than 10 percent of the cone population, and were not targeted.

The researchers tested the effectiveness of the gene therapy both electrophysiologically, by measuring electrical activity in the retinas, and behaviorally, through so-called optomotor response, which tests whether animals will follow a moving stimulus with their heads. By varying the visual stimulus, it is possible to test the animals' acuity.

Electrophysiologically, roughly 80 percent of the treated eyes showed normal responses for up to six months after treatment. The electrophysiological response declined over time, but the authors noted that normal mouse eyes also show weaker electrophysiological responses as they age, and argued that "at least a portion of this loss in treated eyes can be attributed to normal aging effects."

Behaviorally, the researchers managed to restore normal levels of vision to the animals. In human achromatopsia, a visual acuity of 20/200 is typical.

Senior author William Hauswirth told BioWorld Today that though the paper described targeting a disease that affects cones from the outset, the major causes of blindness, such as age-related macular degeneration and diabetic retinopathy, primarily affect rods. However, he said, "cones go once rods go; every blinding disease happens because you lose your cones." The experiments suggested that it might be possible to prevent such secondary cone death in diseases that primarily affect rods.

Hauswirth is co-founder of Alachua, Fla-based Applied Genetic Technologies Corp., which aims to use adeno-associated virus-based gene therapy for the treatment of degenerative eye disease, among other things. (See BioWorld Today, Dec. 4, 2006.)

According to the paper's conflict-of-interest statement, AGTC "might, in the future, commercialize some aspects of this work." For the time being, however, though Hauswirth does have a financial interest in AGTC and the use of recombinant AAV vectors in general, no licensing or other financial agreement regarding that particular research exists.