Genes that encode what are called “complement” immune factors are linked to the breakdown of the retina in multiple sclerosis (MS) patients — a measure that, in turn, predicts brain damage and loss of eyesight.
The study, a joint effort between researchers from Johns Hopkins School of Medicine, Harvard Medical School, and the Broad Institute, was presented at the Young Scientific Investigators Session 1 at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2016 Congress Sept. 14-17 in London.
Titled “A network approach to suggest a role of variation in complement pathway genes in retinal atrophy in multiple sclerosis patients,” the study had an ambitious approach, in which researchers used imaging data from eye examinations to identify genes involved in the severity and disease course of MS.
The researchers’ findings present new insights into the disease processes that lead to degeneration of the eye and brain tissue in MS patients.
While whole-genome analyses have identified more than 100 gene variants associated with an increased risk of developing MS, few genetic factors that affect the severity of the disease have been found.
The research team followed 382 MS patients of European descent, and repeatedly measured the thickness of two layers of the patients’ retina, known as the ganglion layer and the inner plexiform layer. To obtain accurate measurements, researchers used a method called optical coherence tomography (OCT) imaging.
Patients were followed for an average of 3.5 years, which allowed researchers to model individual disease trajectories. Researchers then performed a genetic analysis, screening for gene variants that were associated to the disease courses.
An advanced statistical analysis allowed the team to describe a genetic network composed of 18 genes. It became clear to the team that the network was centered around the complement system — a part of the immune system that enhances, or complements, the ability of immune cells to perform their job. In particular, a complement factor known as C3 was found to be more strongly associated with a thinning of the retina.
“These results suggest potentially a novel role of the complement pathway that may underlie changes in the retina of MS patients and are supported by existing knowledge of the function of complement genes in retinal ganglion cell pathology and in other neurodegenerative diseases,” the researchers wrote in the Congress’s abstract.