Is Inflammation the Answer? A Potential Future Treatment for Age-Related Macular Degeneration

There is strong evidence that inflammation plays a role in the development and progression of age-related macular degeneration. Now, a drug approved to treat autoimmune diseases such as psoriasis and multiple sclerosis has shown promise in blocking inflammation linked to age-related macular degeneration.

A research team studied inflammation of the retinal pigment epithelium, a layer of cells next to the retina that’s believed to be where age-related macular degeneration begins.

The research was led by BrightFocus Foundation Macular Degeneration Research grantee Daisy Yao Shu, PhD, of the Schepens Eye Research Institute of Mass Eye and Ear in the Department of Ophthalmology at Harvard Medical School.

The team focused on the role of tumor necrosis factor-alpha (TNFα), a pro-inflammatory factor that may be related to the development and progression of age-related macular degeneration and treatment with an anti-inflammatory drug called dimethyl fumarate (DMFu).

Targeting the eye’s inflammatory pathway

The retinal pigment epithelium acts as a gatekeeper of sorts between the light-sensitive photoreceptors of the retina and the layer of blood cells that lie below, called the choroid. Dysfunction within the retinal pigment epithelium is a key feature of age-related macular degeneration, which is a leading cause of blindness in developed countries. Diminishing inflammation and controlling the immune system within the retina could be helpful therapeutic approaches.

Tumor necrosis factor-alpha is a protein that triggers the body’s inflammatory response. People with immune system diseases like rheumatoid arthritis have too much TNFα in their blood, which leads to inflammation and painful symptoms.

TNFα was found to decrease the expression of genes that regulate the way cells work within the retinal pigment epithelium. It caused changes to cells’ mitochondria, which are structures in the fluid of a cell that make most of the cell’s energy, as well as to their metabolism, the chemical changes that take place within cells.

DMFu, the anti-inflammatory drug, is in a class of medications called Nrf2 activators. In multiple sclerosis, it works by decreasing inflammation and preventing nerve damage. It is also approved as a first-line treatment for the skin disease psoriasis.

The research team found that pre-treating the retinal pigment epithelium cells with DMFu blocked the damaging inflammatory effects of TNFα. It normalized both the imbalance of the mitochondria and the metabolic function of cells within the retinal pigment epithelium.

“Our results indicate that DMFu serves as a novel therapeutic avenue for combating inflammatory activation and metabolic dysfunction of retinal pigment epithelium in age-related macular degeneration,” Dr. Shu stated in a summary of the research.

What’s next?

The research team concluded that DMFu serves as a promising therapeutic option for combating TNFα-induced inflammation in age-related macular degeneration.

The research and development of new drugs plays a major role in disease treatment. However, drug repurposing, such as in the DMFu study, is believed to be a more efficient and cost-effective process. That’s because important aspects of a drug, such as its safety, effectiveness, and how it works in the body, have already been established.

Dr. Shu’s BrightFocus-funded research focuses on the retinal pigment epithelium and how to unravel the mechanisms governing the interplay between inflammation and cell dysfunction within it. She seeks to find new ways to dampen this inflammatory response, opening new paths for treating age-related macular degeneration.

Research published

The results of the study were published in the scientific journal Frontiers in Molecular Neuroscience.