Credit: ©Greg Nicholas

Collaborators at two major research institutions in the US have shown that gene therapy can target cone cells and rescue electrical response and visual acuity in a mouse model of achromatopsia, a disorder causing hereditary blindness in roughly 1 of every 30,000 humans.

Achromatopsia is the result of cone vision loss and leads to nearly complete color blindness and poor central vision in most of those who suffer from the disease.

Mice carrying a mutation in the gene Gnat2, which encodes a guanine nucleotide binding protein, have a phenotype similar to that of humans with complete achromatopsia. William W. Hauswirth of the University of Florida College of Medicine (Gainesville) and his colleagues at The Jackson Laboratory (Bar Harbor, ME) used an adenovirus vector to deliver wildtype Gnat2 under the control of a cone-specific promoter into the subretinal space of mutant mouse eyes roughly one month after birth. At 1–2 months after treatment, 19 of 21 eyes responded to the gene therapy, and 17 of those showed electroretinogram (ERG) signals comparable to wildtype mice (Nat. Med., doi:10.1038/nm1596, published online 21 May). In addition, 18 of 21 treated eyes continued to have measurable ERG signals 5–6 months after treatment, 17 of which were still in the normal range. The same gene therapy methodology also rescued the ERG signals in 9-month-old mice.

The researchers used a behavioral test to determine whether the ERG restoration was associated with changes in visual acuity. They found that visual acuity improved in eyes treated with wildtype Gnat2 but not in untreated eyes. In fact, mean visual acuity was not significantly different in treated versus wildtype eyes.

To date, this is the first time cone-targeted gene therapy has been used to restore visual function in an animal model of achromatopsia. As such, this research has important implications for treating various forms of human blindness. “Clinically, this work may directly impact human achromatopsia in a few years,” Hauswirth tells Lab Animal. “More broadly, this work opens up the possibility of helping cones survive the most prevalent causes of blindness in the US—age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa—none of which initially affect cones but all of which eventually lead to cone loss, the final event leading to blindness.” Hauswirth and colleagues are now working to confirm this approach in a dog model that represents the most common form of human achromatopsia.