About Dry AMD
About Dry Age-Related Macular Degeneration Symptoms
Dry age-related macular degeneration (AMD) is a leading cause of blindness impacting more than five million people worldwide, which can severely impair visual function, independence, and quality of life. Dry AMD is a progressive retinal disease in which the photoreceptors, which are specialized neurons found in the retina that convert light into electrical signals required for normal visual function, suffer progressive damage and death, leading to progressive loss of vision.
One of the earliest dry age-related macular degeneration symptoms and signs of photoreceptor dysfunction is progressive damage to, or attenuation of, the ellipsoid zone (EZ), which is a mitochondrial-rich layer of the photoreceptors. EZ attenuation has been shown to precede and predict visual dysfunction in dry AMD and other retinal diseases.
Dry Age-Related Macular
Degeneration Symptoms & Stages
Dry AMD happens in three stages: early, intermediate, and late. It usually progresses slowly over several years. All AMD starts as the dry form, which may progress from early to intermediate and advanced stages, the last of which is called geographic atrophy. In dry AMD, the waste material generated by the intense metabolic activity of photoreceptors in the retina accumulates behind the macula and forms deposits called drusen.
Early
Early dry AMD is usually asymptomatic and is often diagnosed at a routine dilated eye exam based on the discovery of the presence of medium-sized drusen. Loss of dark adaptation may accelerate at this stage.
Intermediate
AMD is considered at the intermediate stage if large drusen are detected and/or your doctor detects any retinal pigment abnormalities. Changes in retinal pigment occur as we age but are accelerated in AMD. This stage may still be asymptomatic for some patients, but many patients experience diminished contrast sensitivity or a blurred spot in their central vision. These changes could lead to visual distortions, blurred type when reading, a sense that colors are no longer as vibrant as they used to be, and difficulty seeing in low light conditions.
Advanced or Late
For subjects not enrolling in the open-label extension, the 4-week Safety Follow-Up Period will begin after the masked treatment period is completed. Subjects will return to the clinical site on Week 76 for a final safety assessment.
Mitochondrial Dysfunction in AMD
Dry age-related macular degeneration primarily affects the macula, a small round area in the retina’s center responsible for visual acuity (the ability of the eye to distinguish shapes and the details of objects at a given distance) and color vision.
The macula is rich with specialized cells, called photoreceptors, that convert light into chemical and neural signals that are then sent to the visual centers in the brain, a process known as phototransduction. Phototransduction and the function of photoreceptors require high levels of energy, which is supported by densely packed mitochondria within the ellipsoid zone of photoreceptors.
Mitochondria are intracellular organelles necessary for cell survival, supporting the function of every organ system in the body, including the eyes. The mitochondria are critical structures that power the cells in the eyes (rods and cones) and enable us to see. In AMD, several environmental and genetic risk factors are linked to increased oxidative stress, creating high levels of reactive oxygen species (ROS) that damage proteins and membrane lipids within the cell, which can lead to inflammation, fibrosis, senescence, and cell death.
When mitochondria become dysfunctional or impaired due to high levels of ROS, this limits their ability to produce ATP. High levels of ROS can damage proteins and membrane lipids within the cell, which can lead to inflammation, fibrosis, senescence, and cell death, implicated in many human diseases, including AMD.
In AMD, mitochondrial dysfunction ultimately leads to the degeneration and loss of photoreceptors within the macula, resulting in the central vision loss. In these clinical trials, the investigational therapy targets the mitochondrial membrane and binds to the cardiolipin to normalize mitochondrial structure and function and improve cell viability and organ function.
- Kaarniranta, et al. Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration. Prog Retin Eye Res. 2020;79:100858.
- Patananan AN, Sercel AJ, Teitell MA. More than a powerplant: the influence of mitochondrial transfer on the epigenome. Curr Opin Physiol. 2018 ;3:16-24
- Chicco AJ, Sparagna GC. Role of cardiolipin alterations in mitochondrial dysfunction and disease. Am J Physiol Cell Physiol. 2007;292(1):C33-44.