Molecular "sunglasses" against macular degeneration
Molecules that suppress the production of toxic byproducts of the functioning of retinal photoreceptor cells and thus reduce its sensitivity to light are being tested on patients with age-associated macular degeneration (retinal dystrophy) – the main cause of blindness in people over the age of 50. If successful, the tested drug will solve the serious problem of treating this disease, which affects more than 15 million people in the United States alone.
With macular dystrophy, the cells of the central part of the retina, the macula, or macula, are destroyed, gradually leading to the loss of central vision, and subsequently to complete blindness. A characteristic feature of the dry form of macular degeneration is the so–called druses, areas of the destroyed retina of yellow color. As the disease progresses, they gradually merge.
In recent years, several drugs have received official approval for the treatment of a more severe form of the disease – wet macular dystrophy. However, effective methods of treating a more common form – dry macular dystrophy, which accounts for about 90% of cases of the disease – do not exist today. Some cases of dry macular degeneration gradually turn into wet, so its effective treatment would solve two problems at once: suppressing the early symptoms of the disease and preventing the progression of the disease into a wet form.
While scientists are trying to understand the causes of age-associated macular degeneration (the main risk factor is considered to be age, to which genetic predisposition and lifestyle factors are added: exposure to ultraviolet light and a lack of vitamins A, E, C, beta-carotene, as well as zinc), there is gradually growing evidence that the accumulation in the tissues of the eye certain compounds can stimulate the destruction of cells underlying the development of the disease. These compounds accumulate in photoreceptors – light–catching cells of the retina - during the normal functioning of the eye, as the photosensitive pigments of the cells change their conformation (spatial structure) under the influence of light.
One of the forms of pigment, which is a derivative of vitamin A, is highly reactive and penetrates into the surrounding tissue – the retinal pigment epithelium. Over time, this can lead to the death of epithelial cells, and subsequently photoreceptors, the normal functioning of which is impossible without the epithelium.
Disappearing vision: photoreceptor cells (in the form of tubes) during the normal functioning of the eye
produce a toxic by-product (yellow specks) capable of damaging retinal cells,
which leads to the development of macular degeneration.
Changing the conformations of pigment molecules is necessary for light perception, however, researchers believe that slowing down the transformation cycle in photoreceptors responsible for night vision – the so–called rods - can slow down the damage process without weakening daytime vision. (Preliminary results suggest that this may impair adaptation to darkness.) According to ophthalmologist Ryo Kubota, who is the founder of the Seattle-based recently established company Acucela, specializing in the development of methods for the treatment of macular dystrophy, during the daytime, the rods work extremely actively, wasting a huge amount of vitamin A in vain, since daytime color vision is completely provided by another type of photoreceptors – cones.
One of the compounds currently undergoing clinical trials, developed by Acucela specialists, suppresses the work of an enzyme that converts a photopigment in photoreceptors from one form to another. This process occurs exclusively in the tissues of the eye, which makes it possible to take the drug systematically without affecting other tissues. The initial safety test of the drug in humans has been successfully completed, and in the coming weeks the company plans to begin clinical studies of its effectiveness in patients with late stages of dry macular degeneration. It is also planned to test this drug as a treatment for diabetic retinopathy and Stargardt's disease, a rare hereditary form of macular dystrophy.
The Florida-based pharmaceutical company Sirion Therapeutics is testing another drug based on a different mechanism of action. This compound is a synthetic derivative of vitamin A, which suppresses the accumulation of toxins by binding one of the proteins involved in the process. According to preliminary results of testing in patients with late stages of dry macular degeneration, the drug reduces the rate of formation of retinal scars characteristic of this disease by 45%. However, until the end of the studies scheduled for next year, experts are not sure of the statistical reliability of these results. Given that there are currently no officially approved treatments for age-related dry macular degeneration, the U.S. Food and Drug Administration (FDA) intends to consider approving this drug as soon as possible.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Technology Review: Molecular Sunglasses for Macular Degeneration.
05.11.2009