Parsing Proteins and Closing Holes

Published in Wilmer - Annual Report 2020

For some eye conditions, like detached retina, the name is literal. For others, like floaters, the descriptions are more figurative. For the condition known as idiopathic macular hole, it is a bit of both. First, there is an actual hole in the fovea, the anatomic center of the macula and the precise spot in the eye where fine detail is resolved. Then, there is a hole in the figurative sense of the condition’s effect on the patient’s vision.

“With a macular hole, the defect in central vision precludes seeing the thing that you’re trying hardest to focus on,” says Sharon Solomon, M.D., Wilmer’s Katharine M. Graham Professor of Ophthalmology and an eye surgeon who is an expert in idiopathic macular holes.

How exactly do macular holes affect reading vision? “Imagine reading the word ‘T-H-E’ one letter at a time,” she says. “For those with macular holes, the ‘T’ will be distorted or missing altogether as the object of focus, like it fell into a hole.”

The problem can be corrected with surgery, but the recovery is intensive, requiring the patient to lie face down for up to a week. “And when we say, ‘face down,’ we mean your face is parallel to the floor, except when you come up to eat. That’s 24 hours per day for a good five to seven days,” says Solomon.

No one knows exactly what causes idiopathic macular holes or why the prevalence is so much higher in women. Solomon has collaborated with scientists at Wilmer to find out.

Colleagues Richard Semba, M.D.,M.P.H., Wilmer’s W. Richard Green Professor of Ophthalmology, and Pingbo Zhang, Ph.D., world experts in the field of proteomics (the study of proteins in living organisms), have helped Solomon elevate this translational research from an idea to a reality.

As she performed surgery and observed the abnormal interaction that the vitreous gel — the transparent colloid that fills the back of the eye — has with the retina, Solomon theorized that perhaps it is the proteins in the vitreous gel that can predispose the patient to developing this blinding condition.

Solomon and the Semba lab embarked on a pilot study to learn how the vitreous of eyes with idiopathic macular holes differs from the vitreous of eyes with normal retinas.

“There are thousands of proteins in the vitreous,” Solomon says. “Any combination of them could affect a biological pathway that results in the formation of idiopathic macular holes.”

Solomon, Semba and Zhang are the first to identify and publish data demonstrating that there are clusters of proteins that are upregulated or downregulated in the vitreous of eyes with idiopathic macular holes compared with eyes with normal retinas. This research has caught the attention of the National Eye Institute (NEI), as there is now the potential to identify the pathophysiology of this disease process and to possibly develop a marker for disease and a nonsurgical therapeutic intervention.

Solomon is now the national protocol chair of an NEI-sponsored study coordinated by the Jaeb Center for Health Research that plans to narrow the list of likely protein candidates while simultaneously establishing a vitreous biobank for future research.

One patient with particular interest in this research was known for a time by the rather intriguing alias “Patient 007.” Long since self-identified, Marie- Christine Aquarone, a marine scientist, earned the moniker as one of the first to donate her vitreous to Solomon’s study. She has had two holes repaired by Solomon — a macular hole in her right eye in 2013 and a lamellar hole in her left in September 2020.

“Dr. Solomon is truly unique in the medical field, a real gem,” Aquarone says of her decision to choose Solomon as her surgeon and to join the scientist’s important study. “She combines so many great qualities: a doctor who is kind, efficient and thorough, with a great bedside manner, a great researcher, terrific surgeon and excellent teacher.”

Another key aspect to realizing translational research like this is funding. For that, Solomon has had the good fortune to enjoy the support of longtime patients, including Thomas O’Neil and Steven Koren.

O’Neil was driving to work about five years ago when his vision suddenly blurred. He had a detached retina. Solomon saw the distressed O’Neil immediately. “She took one look and said she could save my vision … if we operate tonight,’” O’Neil recalls. An operating room was booked for 10 p.m. At 1 a.m., Solomon completed the surgery that saved O’Neil’s sight.

“I was just very grateful and wanted to express that sentiment with a substantial gift to Wilmer in her name,” O’Neil says.

Like O’Neil, the Korens have become grateful patients of Solomon’s — impressed by her deft clinical skills and bedside manner. One day during a routine visit, the conversation turned to her research. “It didn’t really matter what she was studying; we wanted to help,” says Steven Koren. “We have total confidence in Sharon Solomon.”

Gifts like those from the O’Neils, Korens and others allow Solomon the freedom to pursue her research ideas unencumbered by the traditional restrictions of having to first present preliminary data to acquire funding.

“Too often, as a clinician, you have ideas on how to fix things, or at least make them better, but you don’t have the time, resources or support to get the job done,” Solomon says. “Donors make it all possible.”