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There’s More Than What Meets the Eye

02/29/2016

Tufts MC researcher’s groundbreaking basic science and clinical studies are shedding new light on an often underappreciated component of the eye

When Ophthalmologist and Cornea Specialist Pedram Hamrah, MD, FACS joined the New England Eye Center (NEEC) at Tufts Medical Center last summer, he brought with him a unique skill set and a thriving research portfolio—with funding from the National Institutes of Health (NIH), foundations, philanthropy and several industry partners—dedicated to studying the cornea, the transparent layer in the front of the eye. With Dr. Hamrah’s corneal expertise, the NEEC is now one of only a few centers in the country with the ability to image and analyze the entire eye at a precise level of detail.

Translational Immunology Research
Dendritic Cells

Until recently, the cornea was thought to be a passive fibrous tissue with no active immune system. However, the discovery 13 years ago of dendritic cells residing in the central cornea changed that opinion in the field and has resulted in a massive shift in thinking.

“Dendritic cells are like the police of the cornea’s immune system,” said Dr. Hamrah. “They identify infections or foreign substances in the eye and present the information to other inflammatory cells, which then attack and eliminate the intruders. The more we learn about dendritic cells, the clearer it becomes that the cornea’s immune system is highly active rather than reactive.”

Dr. Hamrah has been at the forefront of exciting research on the function of dendritic cells since 2007. He has applied a new imaging technique to the eye (called multiphoton intravital microscopy), which allows for the precise examination of the cornea and the blood vessels around it. With funding from the National Eye Institute (NEI) of the NIH and a Research to Prevent Blindness grant, Dr. Hamrah has used this technology to characterize cell behavior and interaction between immune cells and blood vessels under normal conditions, during inflammation and after corneal transplantation, as well as identify the mechanism of the cells’ recruitment to the cornea.

Plasmacytoid Dendritic Cells

Dr. Hamrah also recently discovered a new resident cell type in the cornea called plasmacytoid dendritic cells (pDCs) that appear to be important mediators of anti-viral immunity; his group has recently shown that these cells prevent inappropriate activation of inflammation in the cornea, blocking unnecessary attacks on the eye and keeping it clear and functional. These cells serve to protect and maintain corneal nerves, and can even regenerate them, if necessary. Dr. Hamrah’s studies have demonstrated the presence of these cells and their increase in number during inflammation stemming from both infectious diseases and autoimmune diseases. This research into the function of pDCs and their role in corneal immunity may result in the development of novel drugs for the treatment of pathological eye conditions, including neurotrophic keratitis and dry eye disease.

Relationship Between Immune and Nervous Systems

In addition, Dr. Hamrah’s group is investigating the fascinating relationship between the immune and nervous systems, by studying the immune system’s function in nerve regeneration and the role of the nervous system in regulating the immune system.

“If the cornea’s nervous system is functioning normally, nerves prevent inflammation and unnecessary attacks, while immune cells in the cornea, particularly plasmacytoid dendritic cells, maintain and regenerate corneal nerves,” said Dr. Hamrah. “But if the corneal nerves are damaged, we see inflammation, scarring and disintegration occur.” 

Clinical Research

Dr. Hamrah also leads a very active clinical research center, with the goal of bringing new therapies directly to patients. This research is focused on using live imaging—called in vivo confocal microscopy—to better understand molecular and cellular mechanisms in corneal immunology, neuro-immunology and inflammation. This technology, now available in the NEEC clinics at Tufts MC, was funded with two generous grants from the Lions Club International Fund and the Massachusetts Lions Presidential Award. With an 800x magnification and a high resolution of 1 micron, Dr. Hamrah and his colleagues use this specialized microscope to do noninvasive optical biopsies of the cornea and eyelids to better understand corneal and ocular surface disease at a cellular level. By identifying inflammation in cells in the eye and determining the level of inflammation in the cornea, Dr. Hamrah can provide personalized treatment to patients with corneal and ocular surface diseases. With industry support, Dr. Hamrah has initiated and participated in several clinical trials to examine the efficacy of various anti-inflammatory and regenerative medications on patients with these conditions, and assess the impact of these drugs on cellular changes.

“I came to Tufts MC to take my imaging research to the next level, especially on the clinical side,” said Dr. Hamrah. “It was a great opportunity to expand my studies and use my corneal clinical research skills and experience to help the New England Eye Center and its Boston Image Reading Center expand nationally and internationally in the areas of cornea and ocular surface. There is still much work to do to fully understand how the cornea works, but we are making great progress.”