Molecular Sunglasses for Macular Degeneration

Dampening a light-sensing reaction in the eye might slow a common cause of blindness. 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.

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.”

While this reaction is vital for sight, researchers believe that slowing the cycle in the subset of photoreceptors responsible for night vision, known as rods, could slow damage without having a large impact on daytime vision.

One compound developed by Acucela that is in clinical trials inhibits the enzyme that converts the photopigment in photoreceptors from one form to another. This process happens only in the eye, allowing the drug to be administered systemically without affecting other tissue.

A second drug that acts by a slightly different mechanism is being evaluated for macular degeneration by Sirion Therapeutics, a Florida-based pharmaceutical company. The compound is a synthetic vitamin A derivative that is thought to reduce toxin buildup by binding to one of the proteins involved in the reaction. According to preliminary results from tests of the drug in patients with late-stage dry macular degeneration, it can slow the scarring that is characteristic of the disease by 45 percent. However, scientists won’t know if the results are statistically significant until completion of the study next year. Because no treatments have been approved for dry AMD, the U.S. Food and Drug Administration has fast-tracked the drug, speeding the review process.



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