Scientists get one step closer to reversing retinal degenerative diseases

Degenerative disorders affecting the retinal pigment epithelium (RPE), such as age-related macular degeneration and autosomal recessive bestrophinopathy, can ultimately lead to blindness. Some of these life-changing disorders are the result of mutations in a single gene, called BEST1.

Although the genetic defect in BEST1 was identified almost two decades ago, its physiological role-;how it does what it does, was unclear. Now, researchers from Columbia University and University of Rochester have used a novel approach to solve this mystery. Today, they published their pioneering study in the journal eLife.

The researchers created a "disease-in-a-dish," meaning that they coaxed skin cells taken from an adult patient first back into an embryonic-like state (called induced pluripotent stem cells, or iPSCs) and then into RPE cells to create a model of retinal degenerative disease. Then they assessed physiological properties of the RPE cells carrying normal or mutated BEST1 via innovative, interdisciplinary approaches to pinpoint the exact role of the BEST1 gene.

The researchers were also able to show that RPE cells that carry the BEST1 gene mutations, which are the same cells that are damaged by degenerative diseases, can have their damage reversed by providing healthy copies of the BEST1 gene (through viral gene supplementation, which uses a specially selected virus to "carry" new genes into the cells).

"Our team provided evidence that autosomal recessive bestrophinopathy is a 'chloride channelopathy' and is a treatable disorder," said RPB Physician-Scientist Awardee Stephen H. Tsang, MD, PhD, Associate Professor of Ophthalmology and Associate Professor of Pathology and Cell Biology at Columbia University, and Tingting Yang, PhD, Assistant Professor of Pharmacology and Physiology at University of Rochester.​