Molecules designed to slow the production of toxic byproducts in the eye by making it less sensitive to light are now being tested in patients with macular degeneration, the leading cause of blindness in people age 50 and older. If successful, the compounds would provide a much needed therapy for the disease, which affects more than 15 million people in the United States.
In macular degeneration, cells in the center of the eye, called the macula, deteriorate. A handful of new treatments for the more severe form of the disease, known as wet AMD, have been approved in recent years. But no treatments are yet available for the dry form, which accounts for about 90 percent of cases. Some dry cases ultimately progress to the wet form, which accounts for a large part of AMD-related blindness. “If you can treat dry AMD, you can kill two birds with one stone,” both reducing early symptoms and preventing progression to the wet form, says Paul Sieving, director of the National Eye Institute, in Bethesda, MD.
While scientists are still trying to understand the causes of AMD–age is the biggest risk factor, with genetics and lifestyle factors also playing a role–a growing pool of evidence suggests that the build up of specific compounds in the eye can hasten the cellular damage that underlies the disease. These compounds accumulate in the photoreceptors–cells in the retina that detect light–during normal eye function as the light-sensitive pigments in these cells change conformation in response to photons.
One form of the photopigment, a derivative of vitamin A, is highly reactive and leaks into nearby tissue called the retinal pigment epithelium. “Over time we think these compounds are a burden for the retinal pigment epithelium, which is essential for the healthy function of the photoreceptors,” says Janet Sparrow, director of the Retinal Cell Biology Laboratory at Columbia University, in New York. “In age-related macular degeneration, particularly the dry form, these cells die, and the photoreceptors follow.”