Using a newly developed genetic therapy, researchers at the University of Pennsylvania have successfully corrected both mild and severe ocular lesions in canines with Best disease. The investigators say the success shows promise that a similar approach could work in humans.

Best disease (vitelliform macular degeneration), a congenital disorder that primarily affects the central vision of children and young adults, can lead to blindness. It is associated with mutations of the BEST1 gene, which cause retinal detachment and photoreceptor (PR) cell degeneration due to a primary channelopathy in neighboring retinal pigment epithelium (RPE) cells, the study says.

The research, published in the Proceedings of the National Academy of Sciences, used in vivo imaging to first show RPE/PR microdetachment across the retina, which contracted with dark adaptation and expanded upon exposure to a moderate intensity of light. Subretinal BEST1 gene augmentation therapy reversed not only clinically detectable subretinal lesions but also the diffuse microdetachments, according the study.  

In addition to offering a development pathway that may one day lead to therapies for human eyes, the study also helps clarify the course of the damage to the RPE. “Since we understand the mechanism of disease better than before, it also allows us to understand the mechanism of rescue,” lead researcher Karina E. Guziewicz, PhD, said in a press release. “We can visualize these projections extending from the RPE that never existed before; it’s incredible. That restored the proper apposition between those two cell layers.”2

1. Guziewicz KE, Cideciyan AV, Beltran WA, et al. BEST1 gene therapy corrects a diffuse retina-wide microdetachment modulated by light exposure. PNAS. March 5, 2018. [Epub ahead of print]. 

2. Baillie KU. New gene therapy corrects a form of inherited macular degeneration in canine model. March 5, 2018. Accessed April 4, 2018.