Making the Invisible Visible

Poets and artists as far back as Leonardo Da Vinci and William Shakespeare have described the eyes as windows to the soul. For ophthalmologist Robert C. Sergott, MD, this sentiment should be altered to reflect a stunning medical fact — in actuality, the eyes are truly a window to the brain.

The Margaret and Richard Hayne Distinguished Professor of Ophthalmology in the Department of Neurosurgery at Sidney Kimmel Medical College and the founder and executive director of Jefferson’s William H. Annesley Jr. MD ’48 EyeBrain Center, Sergott serves as director of neuro-ophthalmology at Wills Eye Hospital.

Sergott’s motivation to make a difference in the medical field started early and close to home. His mother was a nurse who taught obstetrics and gynecology nursing at Penn Presbyterian Medical Center and Lankenau Hospital. As a child, he suffered from painful ear infections, and he recalls regular drives from the Philadelphia suburbs to New Jersey to see Michael Rachunis, MD ’36, a Jefferson graduate who never failed to soothe his pain.

“It was the combination of those two early life experiences that created my interest in medicine,” he says. “When I started to look around at career choices, this seemed to be the most worthwhile in terms of being able to help people when they are having troubles.”

Sergott received both his undergraduate and medical degrees from Johns Hopkins University and is grateful for his exposure to and mentorship from his medical school clinicians, researchers, and teachers. “My interests included pediatric, adolescent, and adult patients and involved both medical care as well as surgery,” he shares. “Ophthalmology fit that role and allowed for time to pursue both basic and clinical research. Through some very good mentors, especially ophthalmologist Dr. David Knox, I became enchanted with the neurology of the visual system.”

After completing his internship at Columbia University affiliate Mary Imogene Bassett Hospital and his residency in ophthalmology at Wills Eye Hospital, Sergott served fellowships in neuro-ophthalmology at the University of Miami’s Bascom Palmer Eye Institute and in multiple sclerosis at the University of Pennsylvania.

“That gave me some very solid grounding in basic research and neurodegenerative diseases,” he says. “This was in the days of MS where we didn’t have any medications. I was inspired to not only participate and be deeply involved in clinical care but also to continue with clinical research, because you couldn’t be satisfied with the status quo of how we take care of patients.”

Sergott began a lifelong journey to unite neurosciences and ophthalmology, exploring the revolutionary potential of using neuro-ophthalmology to better understand and treat a myriad of neurological disorders. In 2019, he founded the first facility in the world focused on the visual signatures of neurological diseases. The Annesley EyeBrain Center at Jefferson was named in honor of his mentor, ophthalmology pioneer, professor, and former Wills Eye attending surgeon and alumnus William H. Annesley Jr. MD ’48.

“It became more and more obvious that many patients with visual problems related to MS, Parkinson’s, Alzheimer’s, stroke, and rare neurodegenerations were seeking our help,” he explains. “That translated into an unmet medical need, and that was the motivation for the Annesley EyeBrain Center.”

Partnering with Gyorgy Hajnoczky, MD, PhD, the Raphael Rubin, MD Professor of Pathology, Anatomy, and Cell Biology and director of Thomas Jefferson University’s Mitochondrial Research Center, Sergott studies neuro-ophthalmic mitochondria and molecular signatures of neurodegenerative diseases.

“All diseases in the brain start with mitochondrial dysfunction or this dysfunction amplifies the disease,” he explains. The Center’s team investigates mitochondrial function in the laboratory, maps the development of disease, enrolls patients in clinical trials, and shares insights and discoveries with patients in the clinic in the hopes of predicting and preventing neurological diseases and conditions once thought to be untreatable.

This approach enables earlier diagnoses of neurodegenerative diseases as well as providing insight into how and why the diseases start and how to interrupt them, and helping researchers identify new treatment modalities. Sergott and his team are also reaching across the breadth of Jefferson via exciting partnerships with psychiatry, cardiology, cardiac surgery, neurosurgery, and genetics. “We want to be ahead of the disease and not let the disease get ahead of the patients,” he says. “I believe we have started a platform that will go all throughout the University.”

“Neuro-ophthalmology has often been intriguing and very enchanting, because we could tell through the examination of the eye what might be happening in the brain or the spinal cord,” he says. “This window to the brain has now become even larger with recent technologies. There was disease there, and we couldn’t see it, but today, retinal imaging is remarkable. There are new ways to noninvasively and painlessly image the retina and optic nerve like we couldn’t do before. And it has allowed us to make the invisible visible.”

While it’s impossible to biopsy the brain or the spinal cord without doing damage, thanks to the evolution of basic research over the last three to five years, scientists can take samples from skin, urine, or blood; process and culture them in the laboratory; and from there, grow retinas and parts of the brain that function like biopsied tissue, maintaining all the properties of when they were harvested.

They are also evaluating the mitochondrial function within the retina using 3D, 3-nanometer resolution electron microscopy and fluorescent lifetime imaging microscopy and then correlating these findings with tissue specimens.

“The work we’re doing now with fluorescent lifetime imaging ophthalmoscopy, also called FLIO, enables us to study the metabolism of the retina in real time painlessly and noninvasively,” Sergott says. “We utilize two electron microscopes that enable us to correlate these findings with what happens in human tissue, and we can get down to structural, ultramicroscopic details.”

When describing the success of the Annesley Center, Sergott credits the convergence of his collaborations with Jefferson colleagues across many disciplines, partnerships with medical technology, research, industry, and regulatory agencies, and support from Jefferson leadership and philanthropists Margaret and Richard Hayne.

“I’ve been in medicine a long time,” he shares. “It’s rare that you have this coalition of people coming together with their own expertise, their own critical thinking, all the way from leadership through philanthropy through science. It doesn’t happen often. There is continuing inspiration — that sometimes turns into aspiration — from seeing patients who we have not been able to help.”

When asked to reflect on his legacy and what powers him forward, Sergott says, “First, I took good care of patients. Second, we added some new knowledge to neurology, ophthalmology, and neuro-ophthalmology that enables us to diagnose and treat disease sooner and improve the quality of life for those who are either genetically disposed to these diseases or, unfortunately, acquired them. Part of that legacy too is that this goes on and the journey doesn’t stop with me.”