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The Immune System and Macular Degeneration

Joshua Dunaief, MD, PhD

Scheie Eye Institute, University of Pennsylvania

  • Expert Advice
Published on:
3D rendering of human tissues glowing red from inflammation.

There is strong evidence that inflammation plays a role in the development of age-related macular degeneration (AMD). Learn why our immune system and inflammation contribute to AMD and how exciting research may lead to new, promising treatments.

When the Immune System Attacks Your Own Cells

The immune system is designed to fight off infections. To do this, it must be able to tell the difference between our own cells (and leave them alone) versus invading bacteria or viruses (and attack them). As we age, our cells are altered by “oxidative” damage and accumulation of debris, which can cause the immune system to attack our own cells. Oxidative damage occurs when our bodies produce very reactive molecules that can adversely interact with other molecules inside of our cells. The resulting “inflammation” can contribute to a number of age-related diseases, such as arthritis, heart disease, Alzheimer’s disease, and age-related macular degeneration.


There is strong evidence that inflammation plays a role in AMD. Genetic studies show that certain DNA sequence changes in “complement” genes (a part of the immune system) can significantly alter the risk of AMD. Further, complement proteins have been found in drusen, which are deposits that form under the retinas of patients with AMD. Blood samples from AMD patients have higher levels of complement proteins and other indicators of inflammation including C-reactive protein and interleukin 6. During post mortem examination, eyes that have been donated by people with AMD show retinal invasion by immune cells (view a medical illustration of eye anatomy).

These findings suggest that diminishing inflammation and controlling the immune system within the retina could be helpful therapeutic approaches. The key will be to determine the most effective ways to diminish harmful inflammation without impairing the ability of the body or the eye to fight off infections, or causing other unwanted side effects. 

Researchers have provided increased understanding of the mechanisms by which the immune system injures the retina, as well as model systems for testing potential drugs. Studies have been conducted using human genetics, retinal cells grown in plastic dishes, genetically modified mice, post mortem human retinas that have been donated to research, and human clinical trials.

Possible Treatment

While two phase III trials by Genentech targeting the complement protein called factor D in geographic atrophy patients were not successful, phase II and III trials by Apellis and Iveric Bio targeting complement proteins C3 and C5 suggest they may slow progression of geographic atrophy by about 25 percent. These drugs, which are injected into the eye every month or two, are continuing in phase III clinical trials. .

Steps You Can Take Now

In the meantime, a number of epidemiological studies have shown that diet can influence the risk of AMD. Diet can affect inflammation throughout the body, and diets known to reduce systemic inflammation are associated with decreased AMD risk. These diets are generally Mediterranean-style, which are high in vegetables and fruits, with fish twice a week, and include a moderate amount of nuts, while keeping red meat and processed snack foods to a minimum.

Smoking, a strong risk factor for AMD, causes oxidative damage and inflammation. Smokers should try all possible approaches to quit. Read more about prevention of macular degeneration.

Research in coming years will undoubtedly reveal specific mechanisms of AMD-associated inflammation and provide new treatments to increase the chance that AMD patients will maintain good quality vision.

My brother, David Dunaief, MD, and I have studied the effects of a vegetable-rich diet including a daily smoothie, and published articles showing that it decreases levels of a blood test that measures  inflammation, called C-reactive protein (CRP). This may decrease risk of AMD, as AMD is associated with high CRP, and systemic inflammation.

About the author

Headshot of Dr. Joshua Dunaief

Joshua Dunaief, MD, PhD

Scheie Eye Institute, University of Pennsylvania

Joshua Dunaief, MD, received his BA magna cum laude in Biology from Harvard (1987), MD/PhD from Columbia College of Physicians and Surgeons (1996), completed ophthalmology residency at the Wilmer Eye Institute, Johns Hopkins in 2000, and medical retina fellowship at Scheie Eye Institute, University of Pennsylvania in 2004.

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