Blurred or double vision, and in extreme cases, complete vision loss are amongst the earliest symptoms of multiple sclerosis (MS). In this devastating disease, the body’s own immune system destroys the protective sheath that encases delicate nerve fibers — eventually leading to permanent nerve damage. The degree of symptom severity varies widely amongst MS patients, with very little being known about the genetic factors that influence them.
Johns Hopkins Medicine researchers reported a new way of predicting the progression and intensity of the disease symptoms — by looking into the genes, and the eyes of MS patients. Using this technique, they identified an association between the loss of eyesight and 3 specific genes, from a family of inflammatory proteins known as the complement system.
The researchers used an imaging technology called optical coherence tomography, or OCT, which enables them to take a closer look at the nerve cells in the retinas of patients with MS. They scanned the eyes of these patients periodically from 2010 to 2017, precisely tracking signs of degradation in the back of the eye. Patients were found to lose, on average, a layer of retinal nerve cells about 3 times the width of a human hair every year.
At the same time, DNA from blood samples was extracted and sequenced from these patients to determine whether any genetic factors correlated with diminishing ocular nerve tissue. Screened samples from over 800 MS patients revealed new associations between genetic patterns and a reduction of vision.
Genetic changes in the complement genes C3, C1QA and CR1 were found to be strongly associated with declines in visual clarity. For instance, MS patients with variations in the C1QA complement gene had a 71 percent higher risk of not seeing clearly in low light conditions.
“Complement proteins have traditionally been thought of as part of the immune system, binding to antibodies and helping them kill infected cells in the body,” Calabresi explains, with researchers previously showing that too much complement can wreak havoc on healthy nerves.
Through ongoing studies, the hope is that these developments will enable clinicians to offer more effective, personalized MS treatment programs in the future, customized according to patients’ genetic profiles.
For the 2.3 million living with MS globally, such diagnostic and therapeutic interventions can not come soon enough.