Researchers found no significant difference in the structure of amyloid fibrils accumulated in the eyes and those in the heart of a patient with amyloid transthyretin amyloidosis (ATTR-CM) despite being synthesized in different organs, according to a study recently published in Structure.
The authors stated unequivocally that there were no significant structural differences between amyloid fibers in cardiac and ocular tissue of a patient. The result contradicted previous findings, and the study was the first to analyze ocular and cardiac fibers in the same patient.
What is ATTR-CM?
Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is a rare progressive disease of the heart muscle that leads to congestive heart failure. It occurs when the transthyretin protein produced by the liver is unstable. Symptoms include fatigue; shortness of breath; irregular heart rate or palpitations; swelling of the legs, ankles and stomach; brain fog; wheezing; and dizziness. It often goes underdiagnosed because of a lack of awareness and knowledge of the disease. There is currently no cure for ATTR-CM.
“[A]myloid fibrils from the heart and peripheral nerves in the same patient exhibit a uniform structure,” the authors said. “This finding deepens our understanding of V30M-TTR amyloid deposition, which leads to fatal ATTRv amyloidosis.”
Read more about ATTR-CM signs and symptoms
Researchers aimed to compare the structure of amyloid fibers in the eye with cardiac amyloid fibers in a patient with V30M-type ATTR-CM, a variant characterized by amyloid deposition in peripheral tissues. To this end, they employed cryo-electron microscopy (cryo-EM), an advanced technique that enabled researchers to determine the structure of molecules in three dimensions.
The clinical manifestations of ATTR-CM are a direct consequence of amyloid deposition in cardiac tissue; however, depending on the genetic variant, there can also be amyloid deposition in other organs and tissues.
“More than 150 gene mutations are known to cause ATTRv amyloidosis, and the affected organs vary depending on the mutation, resulting in different disease phenotypes,” the authors said.
More than 90% of amyloid fibrils are produced in the liver; these amyloid fibrils are then secreted into the blood and travel to the heart. But the amyloid fibers observed in the eye are produced directly in the retina, and the amyloid deposition observed in cerebral amyloidosis is produced directly in the brain.
That led to doubt about whether different synthesis sites could alter the structure of the molecule; the study concluded they did not.
