Age-related macular degeneration (AMD) is one of the most common causes of vision loss in older people. It affects the macula, the central area of the retina that contains densely packed cells that provide sharp, detailed color vision. People with this condition usually lose the ability to see objects directly in front of them, although their peripheral vision remains intact. Available therapies can slow the progression of the disease, but none of them can restore lost vision.
What is Age-Related Macular Degeneration?
Age-related macular degeneration (AMD) is an eye disease that primarily affects the macula, the central area of the retina. The macula is responsible for the sharp vision we need for reading, recognizing faces or perceiving colors. AMD causes damage to this central area of vision, while peripheral vision is usually preserved. The disease usually develops with increasing age and is more common in people over the age of 60.
There are two main forms of the disease: dry AMD, which accounts for around 80 to 90 % of cases, and wet AMD, which occurs in 10 to 20 % of cases. In the dry form, deposits form under the retina, known as drusen, and the retina can become thinner over time, leading to a slow loss of vision. The wet form progresses more quickly: new blood vessels grow under the retina, leading to bleeding and scarring, which can quickly impair central vision. Typical symptoms include blurred vision in the center of the image, distorted lines, difficulty reading or recognizing faces. At an advanced stage, the central field of vision can be almost completely lost, while peripheral vision remains intact.
The main risk factors include advanced age, genetic predisposition, smoking, high blood pressure, obesity, an unhealthy diet and chronic inflammation of the retina. Treatment depends on the form of the disease: there is no cure for dry AMD, but certain dietary supplements containing antioxidants and zinc can slow down the progression. Wet AMD can be treated with injections of anti-VEGF drugs or laser therapy. General preventative measures such as a healthy diet, smoking cessation, sun protection and blood pressure control can reduce the risk of the disease. Age-related macular degeneration (AMD) is diagnosed by the doctor primarily through a combination of eye examination, imaging and questioning about symptoms.
Current Treatment Options
Age-related macular degeneration (AMD) is treated differently depending on the form. There is no cure for dry AMD; treatment is aimed at slowing down the progression, usually with antioxidant and zinc supplements and a healthy lifestyle. Wet AMD is actively treated with anti-VEGF injections into the eye to stop the growth of abnormal blood vessels; in some cases, laser or photodynamic therapies are also used. In all cases, regular check-ups with an ophthalmologist are crucial and new research is investigating ways to inhibit inflammation or regenerate the retina.
In age-related macular degeneration (AMD), antioxidants and zinc play an important role in slowing down the progression of the disease, especially in the dry form. AMD is partly associated with oxidative stress in the macula, where free radicals damage the retinal cells. Antioxidants such as vitamin C, vitamin E, lutein and zeaxanthin neutralize these free radicals, while zinc is involved in numerous metabolic processes and supports the retinal cells. Based on the large AREDS study, it has been shown that a combination of these nutrients, often supplemented with copper to prevent zinc deficiency, can delay the progression from moderate to advanced AMD. It is important to note that these supplements do not improve existing vision and are particularly useful for patients with moderate AMD or at high risk. The intake should be supervised by a doctor to avoid interactions and overdoses. Overall, although antioxidants and zinc can slow down the progression of AMD, they do not reverse damage that has already occurred.
Research Into a New Cell-Based Approach
In a study published in Cell Stem Cell, scientists tested retinal pigment epithelial stem cells in a phase 1/2a clinical trial. The cells were derived from post-mortem adult eye tissue. These early-stage studies are designed to determine whether a treatment can be safely administered. AMD occurs in two forms: dry and wet. More than 90 % of patients suffer from the dry form, which occurs when the retinal pigment epithelial cells stop functioning and eventually die. In the early stages of AMD, these cells no longer function properly. In more advanced stages, they die and can no longer regenerate. As the disease worsens, several areas in the central retina lose these important cells.
In the current study, people with advanced dry AMD received transplants of specialized stem cells that originally came from eye bank tissue. These adult stem cells were limited in their function and could only mature into retinal pigment epithelial cells. Six participants received the lowest dose of treatment (50,000 cells) during eye surgery. The procedure proved to be safe, as none of the patients experienced serious inflammation or tumor growth.
Early Signs of Visual Improvement
The participants also showed visual improvement in the treated eye, while their untreated eye showed no such changes. This difference suggests that the technique itself may have therapeutic potential. “Although we were pleased with the safety data, what was exciting was that her vision also improved,” said Dr. Rajesh C. Rao, Leonard G. Miller Professor of Ophthalmology and Vision Sciences and associate professor of pathology and human genetics. “We were surprised by the extent of vision improvement in the most severely affected patients who received adult stem cell transplants. This level of vision improvement has not been seen before in this group of patients with advanced dry AMD.” In a test using a standard vision chart, the low-dose group was able to read 21 additional letters one year after treatment.
The research team is currently monitoring 12 additional participants who received higher doses of 150,000 and 250,000 cells. If no safety issues are found, the researchers plan to move on to later phases of the clinical trial. “We are grateful to all of our participants who are allowing us to better understand whether this intervention is safe enough to be used as a future therapy,” Rao said. “These types of NIH-funded studies can help us provide advanced treatments in the field of regenerative medicine, and we are pleased to be able to conduct this first-in-human clinical trial at the University of Michigan.”
Relieving Inflammation May Help Prevent Premature Macular Degeneration
A recent study at the University of Minnesota investigated how inflammatory processes in the eye contribute to early age-related macular degeneration (AMD) and whether their targeted inhibition can prevent the disease. The focus here is on the so-called NLRP3 inflammasome, a protein complex that triggers inflammation. In particular, the proteins Nlrp3 and caspase-1 (Casp1) play a central role in the activation of pro-inflammatory signals such as interleukin-1β.
The researchers used a mouse model that mimics early AMD and genetically unmodified mice. In both groups, they investigated what happens when Nlrp3 or Casp1 are deactivated. It was found that mice without these inflammatory factors developed significantly fewer basal deposits under the retina – typical early signs of AMD. In addition, the invasion of immune cells into the subretinal tissue was reduced, indicating less inflammatory activity. The activity of microglia, the immune cells in the eye, was also reduced in the mutant mice.
The results suggest that inflammation plays a key role in the development of early AMD and that targeted inhibition of the NLRP3 pathway could be a promising preventive approach. These findings open up prospects for future therapies that aim to intervene in the early stages of the disease before serious vision loss occurs. At the same time, it should be noted that these are animal experiments and it is still unclear how the findings can be transferred to humans. Further research will be needed to test the efficacy and safety of such an anti-inflammatory therapy in humans.