Looking at eye blood vessels may give insight on Fabry stroke risk
Researchers find disease causes small but measurable changes in function
Looking at blood vessels in the eye in people with Fabry disease may give clinicians new insights into problems with blood vessel regulation in the body — and help explain the increased risk of stroke and other complications in Fabry patients.
That’s according to a new study, led by researchers in Germany, that found that Fabry causes small but measurable changes in how blood vessels in the eyes function, especially in men.
“Retinal vessel changes in patients with Fabry’s disease are often subtle and may not be readily detectable during routine clinical examinations. … However, advanced techniques such as dynamic retinal vessel analysis offer a more sensitive approach to identify [such] alterations, which could serve as early biomarkers for [other blood vessel-related] dysfunction associated with the disease,” the team wrote.
The researchers stressed that this pilot study was small, and that more, larger clinical studies are necessary “to confirm and, possibly, to better clarify the revealed findings.”
Still, the team noted that “retinal vessel behavior represents a window to the brain and its specific vasculature” that could help to explain certain complications seen in Fabry disease. The retina is a light-sensitive layer of tissue that lines the back of the eye.
The study, “Multimodal dynamic retinal vessel analysis offers new insights in microvascular defects in Fabry’s disease,” was published in the journal Scientific Reports.
A genetic disease, Fabry is caused by mutations in the GLA gene, which provides instructions to make an enzyme that’s needed to break down certain fatty molecules. In Fabry patients, the enzyme is dysfunctional or absent, so these fatty molecules build up to toxic levels in cells, ultimately driving disease symptoms.
The GLA gene is located on the sex-determining X chromosome; as a result, male Fabry patients generally have more severe disease than their female counterparts.
Data have established that people with Fabry are at increased risk of stroke and other problems related to blood flow in the brain. However, the mechanisms by which Fabry sets the stage for problems with brain blood flow are poorly understood.
Investigating the eye to learn more about changes in the body
To gain more insight, two researchers from FH Aachen University of Applied Sciences and their colleagues conducted detailed analyses of blood vessels in the eyes of 10 Fabry patients — four women and six men. Analyses also were conducted on 10 age- and sex-matched people without Fabry for comparison.
The researchers noted that blood vessels in the eyes “share structural and functional similarities” with vessels in the brain. Given that the eyes are much more easily accessible, this type of analysis, the team noted, can be a useful way to gain insight into the health of blood vessels deeper in the body.
The results of this pilot study suggested sex-specific differences in blood vessel health. One example was shown in a test exposing participants to light.
When the eyes are exposed to a flicker of light, blood vessels tend to dilate or widen. In male Fabry patients, this dilation was markedly wider than in people without Fabry. By comparison, in female Fabry patients, the dilation was reduced.
“The entire patient group showed no significant difference in response to the flicker light compared to the control group,” the researchers wrote.
Changes in eye blood vessels more pronounced in males
The individuals with Fabry also showed changes in the spontaneous movements of blood vessels, with more pronounced alterations seen in male patients. In both male and female Fabry patients, there were changes to the microscopic structure of cells making up the walls of blood vessels, the researchers found.
According to the scientists, these data collectively indicate that Fabry disease causes abnormalities in blood vessels in the eyes — and therefore, likely, also the brain.
While the team was not able to pin down exactly why these abnormalities develop, they proposed several potential explanations. One possibility is that Fabry could cause problems with the muscles that normally help control blood vessel movements. Another is that there could be disturbances in the connections between nerve cells and blood vessels. The buildup of fatty molecules in cells lining blood vessels also may contribute, the researchers noted.
Better understanding these changes could help pave the way toward understanding why Fabry patients are at risk of complications like stroke, the researchers said.
Examination with multimodal retinal vessel analysis represents a practical possibility to investigate [the mechanisms] of Fabry’s disease in more detail and might elucidate the effect of potential therapeutic interventions.
The scientists stressed that this was a pilot study with a very small number of participants, so further work will be needed to validate the results and investigate the underlying mechanisms. Still, the researchers said this study demonstrates that analysis of eye blood vessels in Fabry patients is a tool that can be used in future research.
“Examination with multimodal retinal vessel analysis represents a practical possibility to investigate [the mechanisms] of Fabry’s disease in more detail and might elucidate the effect of potential therapeutic interventions,” the researchers wrote, noting also that “retinal vessels can be recorded noninvasively in real time and dynamic responses to stimuli that affect vessel diameter can be directly visualized.”
Analyses could then help to “demonstrate specific structural and functional retinal microvascular changes in Fabry’s disease,” the scientists wrote.
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