Stuart McKinnon, MD, PhD (Photo courtesy of Glaucoma Research Foundation)
Stuart J. McKinnon, MD, PhD, was awarded the 2016 Shaffer Prize for Research for his project to determine whether therapies can be designed to module the immune system to prevent vision loss and blindness in patients with glaucoma.
Dr. McKinnon received the award for his study “Neuroinflammation: The Role of Lymphocytes in Glaucoma.” Thomas Brunner, president and CEO of the Glaucoma Research Foundation (GRF), presented the award during ceremonies at the Glaucoma 360 Annual Gala on Thursday night.
“The concept of looking at immune system involvement in glaucoma is certainly not new,” Dr. McKinnon said. “It has been around in various permutations for 25 or 30 years. What we are doing that has never been attempted before is to isolate the various components of the immune system and see if any of them are relevant to glaucoma.”
The Shaffer Prize, presented annually by GRF, recognizes a researcher whose project best exemplifies the pursuit of innovative ideas in the quest to better understand glaucoma. Dr. McKinnon is associate professor of ophthalmology and neurobiology at Duke University, Durham, NC.
With funding from the Shaffer Grants for Innovative Glaucoma Research in 2014, Dr. McKinnon has been able to directly test the hypothesis that there is an immune system component that probably derives from the blood stream that is relevant to, necessary to, or even critical to the neurodegenerative process that is glaucoma.
Looking into B cells
Looking into B cells
Other laboratories have looked into the role of B cells, a key component of the immune system, for evidence of specific antibodies or antibody profiles that might allow clinicians to diagnose glaucoma even before the appearance of elevated IOP that is associated with the progression of most types of glaucoma. This is the first systematic attempt to identify other types of immune cells, including T cells and macrophages, which may play a role in the development and progression of glaucoma.
The ultimate goal of the research project, Dr. McKinnon said, is to understand the biological mechanisms that either damage axons in the optic nerve so they are unable to carry visual information to the brain or allow axons to be progressively damaged and vision lost.
“If we can understand the mechanism that underlies neurodegeneration, it is just a matter of time until pharmacology and technology catches up to develop an agent that is neuroprotective,” he said. “We have already seen work in multiple sclerosis (MS).”
Dr. McKinnon’s project uses a strain of mice (Rag1 knockout mice) that have been bred to be immune-deficient. They lack certain types of immune cells called lymphocytes that are normally found in the blood stream. The type main types of lymphocytes are B cells and T cells.
Earlier work showed that the lack of lymphocytes in these Rag1 mice is strongly neuroprotective against glaucoma even when the mice have chronically elevated IOP. Similar mice that are not immune-deficient develop glaucoma and lose vision when they have similarly elevated IOP.
Researchers have isolated B cells and T cells and transferred them back into the immune-deficient Rag1 knockout mice. Some mice received B cells, some received CD4+ T cells, some received CD8+ T cells and some have been left immune-deficient. The mice were then subjected to increased IOP.
Potential RCG therapies
Potential RCG therapies
Researchers should know in about four months whether adding back-specific types of immune cells was followed by increased retinal ganglion cell (RCG) axon loss and loss of vision. Once the mechanism that is responsible for RCG axon damage is known, therapies can be designed to modulate and change the immune system to prevent neuron damage, vision loss, and blindness.
“Looking at the impact of the individual components of the immune system is a larger shift in research that is being seen across many medical specialties,” Dr. McKinnon said. “We have seen it in cancer immunology, chronic neurodegeneration–such as Alzheimer Disease and Parkinson Disease, autoimmune disorders, arthritis and more.”
Research into the effects of the immune system on the nervous system in MS has already produced natalizumab, a monoclonal antibody. Natalizumab counteracts the neuroinflammation that is seen in MS.
It is possible that natalizumab could be neuroprotective against RCG axon damage by reducing inflammation of the optic nerve, Dr. McKinnon said, but the agent can have serious side effects and would not be a practical treatment for glaucoma. Newer generations of current biologic agents and more targeted agents developed in the future could have fewer side effects and be more practical in treating glaucoma.