Retinitis pigmentosa (RP) is an inherited eye disease that damages light sensing cells in the retina, according to the National Eye Institute (NEI). Canines with this disease eventually become blind. There is no cure but a recent study suggests that may not always be the case.

Scientists from the University of Pennsylvania and the University of Florida, Gainesville determined for the first time that gene therapy may be of potential benefit even after there has been significant loss of cells in the eye. (Up to this point, animal studies had shown benefits from gene therapy only when it was used in the earliest stages of the disease.)

The study was published Sept. 10 in Proceedings of the National Academy of Sciences.

“The study shows that a corrective gene can stop the loss of photoreceptors in the retina, and provides good proof of concept for gene therapy at the intermediate stage of the disease, thus widening the therapeutic window,” said Neeraj Agarwal, PhD, a program director at NEI.

Loss of function of the retinitis pigmentosa GTPase Regulator (RPGR) gene, which encodes a protein important for maintaining the health of photoreceptors, is present in patients with RP. These are cells in the retina that absorb and convert light into electrical signals, which are then sent to the brain. The disease damages both types of photoreceptors: rods (which allow us to see in dim and dark light) and cones (which allow for seeing fine detail and color).

To overcome the effects of RPGR mutations, the researchers packaged healthy RPGR genes into an adeno-associated virus whose work was to deliver the genes into retinal cells and for the genes to produce the RPGR protein.

The researchers then tested the gene therapy in a naturally occurring canine form of RPGR X-linked RP that appears among some mixed breeds. Dogs with early to late stages of the disease were treated with the therapy in one eye; the untreated eye was evaluated as the control.

Serial imaging suggested that the therapy halted the thinning of the retinal layer where photoreceptors are located and that commonly degenerates from the disease.

Using immunolabeling, a technique that helps tag features inside cells, the researchers showed that the structure of rod and cone photoreceptors was improved in the treated eye and better preserved when compared to the untreated eye. Electrical recordings from the retina also suggested that the therapy preserved cell function.

Overall, the findings suggest that gene therapy halted disease-associated cell death for at least the length of the 2.5-year study, even in dogs with later-stage disease.

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