Project Wonder - The art of science at the Medical College of Wisconsin

Retina Refuse

What does a basement have in common with a retina?

As we age, it can seem inevitable for our basements to accumulate excessive amounts of clutter. In the common disease of age-related macular degeneration (AMD), which affects nearly 20 million US adults, the back of the retina also becomes a dumping ground for refuse that doesn’t belong anywhere near the eye. And, in the case of AMD, the retinal rubbish is harmful to our health and contributes to the progression of the disease, which is the leading cause of central vision loss and legal blindness.

Scientists do not yet know what causes the progressive stockpiling of pebble-like deposits in the retina of patients suffering from AMD. Francesca Marassi, PhD, MCW professor and chair of biophysics, is working meticulously to better understand the composition and atom-by-atom structure of these wayward biomineral deposits, which are known to contain cholesterol, fats (lipids), proteins and a form of calcium phosphate called hydroxyapatite – the same material that forms healthy teeth and bone.

One of the proteins within the mineral deposits that form in the retina is vitronectin. This protein normally circulates throughout our bloodstream in very high quantities and is known for its ability to make cells more likely to stick together and create more complex arrangements. Following decades of investigation into the precise construction of vitronectin, Dr. Marassi and her team deciphered its atomic makeup in 2019 and reported it in Scientific Advances. They described the protein’s shape as a sticky propeller, which helped explain why it fulfills many different “jobs” in the body as well as clarified its role in guiding the assembly of the cholesterol, fats, proteins and minerals in the retinal deposits that appear as AMD progresses.

Dr. Marassi and an international team recently were awarded a five-year, $13 million program project grant by the National Institutes of Health to expand their studies of misplaced calcified deposits in common diseases of aging. They hypothesize that what they learn may lead to the development of new ways to diagnose, monitor and treat AMD and Alzheimer’s disease, which also is marked by a similar formation of errant mineral deposits in the brain.

Perhaps their work will make possible a treatment that acts as a bit of spring cleaning to clear out the litter in the eyes of patients with AMD – or a way to prevent the junk altogether.

Eye photograph:
Danica Nikezic, Research Technologist III, MCW Department of Ophthalmology and Visual Sciences

Animation and soundtrack:
Alex Boyes