Three Generations of Saving Vision

In Discovery Eye Foundation’s spring e-newlsetter there was an article entitled Surgery for the Surgeon, where a leading ophthalmologist talks about convincing himself to have cataract surgery. That eye doctor was Dr. Nesburn, who was willing to share with us his family’s long tradition of saving vision.

Brainwashed by Medicine

“I was brainwashed from the age of 5,” says Dr. Anthony Nesburn, medical director of The Discovery Eye Foundation (DEF). “My dad would take me on rounds at the hospital and to his office. He introduced me to medicine at a really early age.”

Nesburn saving vision
Dr. Anthony Nesburn in UC Irvine lab
Dr. Henry Nesburn was an ophthalmologist in Los Angeles for more than four decades, and he passed his love of the specialty to his son. “I really looked up to my dad,” the younger Nesburn says. “He loved ophthalmology for the same reasons I do: You get to do medical diagnosis; you get to do wonderful surgery, where you keep people from going blind or restore vision; and you can work with people from newborns to the very elderly — they all need eye care.”

Nesburn received a telegram while he was an undergrad at UCLA, telling him he’d been accepted to Harvard Medical School. His mother started crying: “You’re going to Boston! We’re not going to see you anymore!” While he “was loathe to leave Southern California,” Harvard was too good to pass up.

Drafted by the Army out of his ophthalmology residency at Harvard in 1960, Nesburn joined the Navy instead. He followed in his father’s footsteps again, becoming a Navy flight surgeon. (Henry had volunteered during World War II.)

He went on to a Boston Children’s Hospital fellowship in infectious disease, working with Nobel laureate Dr. John Enders, whose work led to the polio vaccine and changed the face of virology. Nesburn then did his residency at Massachusetts Eye and Ear. “I was part of a special program that allowed us to do research, and I was running a research laboratory while I was a resident,” he says. “It gave me the start I needed.”

“At Mass Eye and Ear, I worked for an up-and-coming ophthalmologist and researcher to prove there was a substance that could treat herpes eye infections. We wrote a paper that included the very first antiviral ever described, and it was against herpes virus. It is the basis for today’s herpes antivirals,” Nesburn says. “I was hooked.”

He went back to Los Angeles and received NIH funding to continue his research on ocular herpes. In 1968, he joined his father’s practice half-time, spending the rest of his time doing research.

Two years later, he received a generous offer, when Rita and Morris Pynoos started DEF to fund his research. The Pynooses were grateful to Nesburn for diagnosing their son, Jon, with keratoconus (KC). “I was a second-year resident at Mass Eye and Ear, and Jon Pynoos was an undergraduate at Harvard. His parents went to see my dad, because Jon couldn’t see well, and no one could figure out what was wrong with his vision. My dad said, ‘Send him over to Tony; he’ll figure out what’s going on!’ I said to myself, ‘Holy mackerel! What happens if he has something really complicated? I’m just a newbie!’” Nesburn remembers. “Jon came in; I looked at him, and the keratoconus was so clear and easy to spot. I couldn’t imagine how his doctors didn’t see it. We got him contact lenses, and he was able to see again. When I came back to LA, the Pynooses wanted to do something to help.”

At first, DEF research focused on KC and the herpes research Nesburn was working on at the time. It soon broadened to include macular degeneration and retinal disease.

“My dad had to retire from the practice of ophthalmology at the age of 70, because of bad age-related macular degeneration (AMD). His mother and older sister had had it, as did several cousins. There was no treatment back then that helped,” Nesburn says.

“AMD is the most common cause of permanent vision loss in the elderly in the developed world. I could see where the need was,” he says. “We moved forward at DEF with two driving mantras: We wanted to do something significant in macular degeneration research and to find the cause of keratoconus.”

As a virologist in research and a corneal surgeon, Nesburn realized he needed a corneal biochemist to help with the KC research. He met Dr. Cristina Kenney at an Association for Research in Vision and Ophthalmology meeting. She joined DEF, and within 15 years, they found the chemical cause of keratoconus; they also got married.

Now nearly 80 years old, Nesburn spends most of his time “wearing three hats”: fundraising for DEF, lab research and clinical practice. His daughter, Kristin, is the third generation to join the family ophthalmology practice.

“While I’m still able, I want to try to make a difference in medicine, particularly in macular degeneration,” Nesburn says. “Macular degeneration affects so many people. This is where I want to put my energy. Luckily, as strong as it is in our family, I don’t have it … yet.

“As a researcher, my interest in putting together a program for macular-degeneration diagnosis and treatment has been because it’s a great public health problem. Yes, if I should ever get it, it might be able to help me or my family, but the first thing, as a scientist, is to try to get something to help humankind. I know it sounds sappy, but it’s true.”

3/26/15


Anthony B. Nesburn, MD, FACSAnthony B. Nesburn, MD, FACS
Medical Director, Discovery Eye Foundation
Professor & Vice Chairman for Research, Ophthalmology
Gavin Herbert Eye Institute, University of CA, Irvine

What Are The Differences In The Immune System of An Age-related Macular Degeneration Patient?

A symposium was held in Bethesda, Maryland at the National Institutes of Health on March 6, 2014.  The purpose was to bring together clinicians and researchers from a wide variety of background to discuss the recently discovered differences in the function of the immune system in patients with age-related macular degeneration (AMD) and how it relates to aging.  These differences are important to understand because they may lead to new therapeutic approaches to treat people which are high risk for AMD.

Courtesy of National Eye Institute, National Institutes of Health - immune system
Courtesy of National Eye Institute, National Institutes of Health

  • Three researchers associated with the Discovery Eye Foundation attended the one-day conference.  Cristina Kenney, MD, PhD, has worked in the field of AMD for over twelve years and is a leading expert on the genetics and molecular changes in the mitochondria as it related to the retinal cell death associated with AMD.
  • Lbachir BenMohamed, PhD, is an expert immunologist with a tremendous understanding of how the immune system responds to infections and stress.
  • Anthony Nesburn, MD, has been involved in AMD research at both the clinical and research levels.

By attending this meeting, all three researchers gained insight into the importance of the immune system with respect to maintaining a healthy retina and slowing the progression of AMD.

The highlights of the meeting were the following:

1.  Emily Chew, MD (National Eye Institute) reviewed the clinical aspects of the disease stressing that there are many stages of AMD.

The early stage of AMD is diagnosed based upon the medium-size drusen (about the width of an average human hair) that can be seen underneath the retina.  There may not be any visual changes in these patients.

The intermediate stage of AMD is when subjects have larger drusen and some degree of retinal pigment epithelial cell drop out.  These patients may not have vision loss or other symptoms.

The late stages of AMD which can be categorized into the dry form (geographic atrophy) which has significant loss of the retinal pigment epithelial cells and overlying photoreceptor cells.  Presently there in no treatment for this type of AMD.

These individuals can have changes that cause decreased vision.  The second form of late AMD is the wet form (neovascular), which has growth of abnormal blood vessels beneath the retina that can cause significant loss of vision.  The treatments for this type of AMD are anti-VEGF medications that block the growth of these vessels and help maintain good visual acuity.

2.  Anand Swaroop, PhD (National Eye Institute) reviewed the genetics of AMD and summarized the work of numerous laboratories.  It is now recognized that there are over 20 different genes associated with AMD.  These genes fall into the categories of those involved with Complement Activation, Cholesterol Pathway, Angiogenesis, Extracellular Matrix and Signaling Pathways.  Many of these genes have additive effects, meaning that if a patient has more than one high risk gene, then the likelihood of developing AMD increases.  While we have learned a lot about the genes that are important, we still do not have any gene therapies that can be used to treat AMD.

3.  Six different speakers presented their data related to animal models of AMD and it was agreed that there is not a “perfect” model because most of the animals do not have a macula, the region of the retina that is affected the most by AMD.  However, there is still a lot to be learned by using the models that we do have because if we can better understand the basic pathways involved, then we can block or modify the pathways to prevent the damage.

4.  Jayakrishna Ambati, PhD (University of Kentucky) presented data showing that there is a deficiency of an enzyme called DICER1 in the retinal pigment epithelial cells which leads to increased activation of inflammation via a protein complex called the inflammasome.  He described some of the signaling pathways which are involved in the inflammasome activation.  This is important because these pathways can become targets for treatment of the dry form of AMD.

5.  Jae Jin Chae, PhD (National Human Genome Research Institute) also talked about the role that inflammation plays in the development of AMD.  The data presented reviewed the pathways involved with activation of the inflammasomes which is the first step in a cascade of events that result in inflammatory diseases.  They have identified a calcium-sensing receptor (CASR) which triggers the activation of the NLRP3, a key component of the inflammasome.  Understanding how this series of events works allows researchers to develop medications to block or interfere with the pathway and therefore decrease the levels of inflammation.  

Dr. M. Cristina KenneyM. Cristina Kenney, MD, PhD
Professor and Director of Ophthalmology Research
School of Medicine, Dept. of Ophthalmology
University of California, Irvine