ACTRIMS 2023: Certain eye cells tied to MS-related changes in study

These cells may play key role in vision changes in MS

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Images of blood vessels and synapses surround the word ACTRIMS in this illustration for the annual forum.

Certain cells in the eyes — specifically blood vessel cells and a type of neurological immune cell called microglia — exhibit high expression or activity of genes that have been linked to multiple sclerosis (MS), a new study reports. 

The researchers also “identified variants of interest that play a causal role in retinal degeneration in MS,” the team wrote.

The results imply that these eye cells may play key roles in the ocular changes that are common among people with MS, which can lead to impaired vision, according to Samantha Hao, a medical student at Johns Hopkins University.

Hao presented the study’s data at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) annual forum, held Feb. 23-25 in San Diego and virtually. Her talk was titled “Integration of MS Risk Genes with Single Cell Transcriptomics in the Retina and Predictors of Retinal Layer Thicknesses.”

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Investigating the mechanisms that impact eye cells

MS is caused by inflammation that damages nerve fibers, and the resulting neurological impairments give rise to a range of disease symptoms. The damage can affect the cells in and around the eye, leading to problems with vision; the majority of MS patients experience some form of vision issues. 

One characteristic feature of MS-related eye damage is degeneration and thinning of cells in the retina, the back part of the eye that houses light-sensing cells (rods and cones). Retinal degeneration is common in MS, affecting nearly all people with the disease, and some data suggest that retinal thinning may predict MS progression.

However, the cellular mechanisms that drive cell degeneration in the retina are incompletely understood. 

To learn more, Hao and her team conducted a series of genetic analyses. First, the researchers analyzed single-cell RNA sequencing data for more than 40,000 retinal cells, including rods and cones, as well as blood vessel cells, microglia, and specialized eye neurons called bipolar cells. Using this type of data, the team identified gene expression profiles — that is, patterns of which genes are turned on or off for each type of cell.

Next, the scientists used data from a large-scale genetic analysis of 14,802 MS patients that identified genes contributing to increased MS risk. Although MS is not directly caused by genetics, a number of genetic factors have been linked to the disorder

Using these two datasets, the team conducted statistical analyses to examine the expression of MS-linked genes in different types of retinal cells. Results showed that microglia and blood vessel cells both exhibited high activity levels of MS-related genes. 

“We found that genes defining these two cell types were significantly enriched in” genetic variations related to MS risk, Hao said.

The findings were replicated when two MS patient groups followed at Johns Hopkins were used for the genetic analysis, with blood vessel cells being significantly associated with retinal thinning in people with MS.

“We found that microglia and vascular cells are implicated in the pathogenesis [disease-causing mechanisms] of MS in the retina,” Hao said.

The finding of microglia was not surprising, according to Hao, as these immune cells are known to play a role in the inflammatory attack that drives MS. These cells also have been previously implicated in MS-related eye damage.

However, the role of blood vessel cells in MS-related eye system damage “is less well-defined than microglia,” Hao said.

She concluded that this finding “reinforces prior evidence of the inflammatory response of retinal microglia in MS,” and said it “suggests that vascular changes are associated with MS in the retina.” The study’s results also imply that “vascular dysfunction plays a role in the neurodegeneration” that occurs in MS, according to Hao.

These findings could be a basis for further studies to better understand the role of these cells in MS-related eye damage, she said.

Note: The Multiple Sclerosis News Today team is providing in-depth coverage of the ACTRIMS Forum 2023 Feb. 23-25. Go here to see the latest stories from the conference. Follow along on Facebook, Twitter, and Instagram for live updates using the hashtag #actrims2023.