New gene therapy cures hereditary retinal dystrophy in dogs
A study published in the Proceedings of the National Academy of Sciences by scientists from the University of Pennsylvania presents the results of gene therapy for Best’s macular degeneration, or yolk-form degeneration of the yellow spot, in a canine model of the disease. This form of retinal degeneration is manifested by the gradual loss of central vision, or visual acuity, the purpose of which is to perceive small objects and their details. The disease is caused by a mutation in a gene called BEST1.
What you will learn in the article
- How Best's macular degeneration causes gradual loss of central vision through a BEST1 gene mutation
- Why University of Pennsylvania researchers compared the retinal connection to a zipper between visual and supporting cells
- How a canine model closely resembling human Best's disease helped researchers test gene therapy
- Why the retinal pigment epithelium and central fossa are important in the disease mechanism
- How a harmless viral carrier delivered a normal BEST1 gene copy to dogs with early or mid-stage disease
Table of Contents
Before embarking on gene therapy experiments, scientists have elucidated the subtle mechanism underlying Best’s disease. “In our eye, there are two layers of retinal cells that butt up against each other, forming a zipper-like connection where the visual cells come together with the supporting cells,” says one of the study’s authors, Artur V. Cideciyan of Penn’s Perelman School of Medicine at the University of Pennsylvania (Penn’s Perelman School of Medicine). – “The disease actually consists of ‘unzipping’ this zipper, and we zipped it,” he explains.
On the left, a retinal slice of an untreated eye of a dog with Best’s macular dystrophy; on the right, a protein expressed by the BEST1 gene after gene therapy is highlighted in red. Figures from the press release New Gene Therapy Corrects a Form of Inherited Macular Degeneration in Canine Model – ВМ.
A team from the University of Pennsylvania has identified in dogs an exact resemblance to human Best’s disease. Earlier, ophthalmologist William Beltran (William Beltran) found that in dogs, as in humans, in the center of the retina is a small area densely packed with light-sensitive cells cones. This area is called the central fossa, and it is the area that is important for visual acuity. But the BEST1 mutation in both humans and dogs causes this fossa to break down over time, leading to vision loss. As shown by co-author Karina E. Guziewicz (Karina E. Guziewicz), assistant professor of veterinary medicine at Penn’s School of Veterinary Medicine, it is associated with underdevelopment of the supporting cell layer – the retinal pigment epithelium, which is in close contact with light-sensitive cells.
Photograph of the dog’s ocular fundus before and 5 years after treatment.
This discovery pointed the way for new gene therapy and changed the view of the disease as a lesion of the entire retina. Using a harmless viral carrier, the authors injected a normal copy of the BEST1 gene – either human or canine – into dogs with a model of early to mid-stage Best’s disease. Subsequent studies showed that the “zipper” between the retinal pigment epithelium and light-sensitive cells was restored in the gene therapy-treated dogs.
This effect has been maintained over the past five years. “Tests of the method for safety for humans should begin in the next two years,” Gutsievich says.
Marina Astvatsaturyan, Echo Moscow
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Key takeaways
- Best's macular degeneration is linked to mutation in the BEST1 gene and gradual loss of visual acuity
- Researchers found that the disease involves disruption of the connection between retinal pigment epithelium and light-sensitive cells
- Dogs were identified as having a close resemblance to the human form of Best's disease
- Gene therapy used a harmless viral carrier to inject a normal human or canine BEST1 gene copy
- The restored “zipper” effect between retinal layers was maintained in treated dogs for five years
Published
June, 2024
Duration of reading
2-3 min
Category
Aging and youth
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