Age-related macular degeneration (ARMD) affects millions of people worldwide, and with a rapidly aging global population, the prevalence of ARMD is expected to nearly double by 2020. ARMD is the leading cause of blindness in the U.S. among people age 65 and over.
Most individuals with ARMD have a progressive degenerative change of both eyes due to damage to the retinal pigment epithelial (RPE) layer under the macula; this termed dry degeneration. Less than 10% of those individuals will progress to choroidal neovascularization resulting in exudation and/or hemorrhage of the macula, wet ARMD. The critical role of the RPE in ARMD is recognized by heroic attempts to move the macula to areas of healthy RPE with macular translocation surgery. Additionally, very recent and limited trials with embryonic stem cells repurposed as RPE cells have been initiated in advanced dry ARMD.
Significant strides have been made in the treatment of wet ARMD – namely intraocular injection of medications that can inhibit the growth of the offending new blood vessels. However, the treatment of dry ARMD has been limited to nutritional therapy. The nutritional therapy is based on the knowledge that there is declining anti-oxidant function in the aging eye. Normal functioning of the retinal RPE produces oxidants, free radicals and reactive oxygen species (ROS) – well managed in youth – but accumulation of these leads to disease in the aged eye.
There is a need to find an effective prevention and/or treatment for ARMD before it evolves to advanced disease. In the normal retina, the RPE performs multiple functions in the retina. During aging and in the presence of disease the robustness of each of these functions diminishes.
Studies of the the RPE indicate that the capacity of the RPE to replace itself in response to injury is compromised with aging.
The Research Plan
Aging or senescence of the retinal pigment epithelium (RPE) is a key contributor to ARMD. Senescence, also known as replicative senescence, refers to the induction of a non-dividing state in otherwise mitotically competent cells. Telomeres are the caps on the end of chromosomes, and telomerase is an enzyme that adds telomeres to the chromosome. Telomere erosion is a major biological trigger for senescence. Telomeres are long stretches of DNA found at the ends of chromosomes that consist of tandem repeats of a short sequence element.
Loss of telomeric DNA occurs during cell division because the end of the lagging strand of the chromosome cannot be fully replicated. In some cells, this loss is partly or completely restored by telomerase.
In this pilot study, forty (40) consecutive individuals will be recruited into the study. Not all individuals who have an interest will qualify for inclusion in the study. To be qualified, applicants will have early ARMD with its primary manifestation of drusen of the macula (fig A). Subjects will be randomized to receive study product or placebo.
1. a complete ophthalmologic examination
2. color photography of the macula
3. optical coherence tomography (OCT) and
4. macular integrity assessment (MAIA) examination (fig B).
All participants will have two qualifying meetings with investigators and all will have at least three additional examination as well as phone calls in the following eighteen months. A participant can choose to leave the study at any time.