A genetic study published in Science Advances has identified inflammation-related proteins that may influence retinal vascular aging, cardiovascular disease risk, and lifespan. Using Mendelian randomization, researchers examined how chronic inflammation (“inflammaging”) affects vascular complexity in the retina – a potential indicator of systemic vascular health.
The study analyzed 74,434 participants from the Canadian Longitudinal Study on Aging, Genetics of Diabetes Audit and Research in Tayside Scotland, and the UK Biobank. Retinal vascular complexity was measured as fractal dimension (Df) from fundus photographs of the rear of the eye, representing microvascular branching patterns linked to aging and disease.
A genome-wide association study (GWAS) identified a new genetic locus near the DAAM1 gene, suggesting a role in determining retinal vascular structure. Lower Df was genetically correlated with cardiovascular disease, stroke, and inflammation, while higher Df correlated with longer lifespan.
By integrating genetic data on 1,159 circulating proteins from the Prospective Urban and Rural Epidemiological (PURE) cohort, the researchers identified eight causal proteins linking inflammation to vascular changes. Among them were matrix metalloproteinase-12 (MMP12) and immunoglobulin G Fc receptor IIb (FcγRIIB), both associated with inflammatory and atherosclerotic activity.
These findings suggest that inflammation contributes to reduced retinal vascular complexity, reflecting systemic microvascular deterioration. The retinal fractal dimension – obtainable through standard optometric imaging – may therefore serve as a noninvasive biomarker for vascular aging and chronic inflammation.
The authors note that while genetic associations can clarify biological pathways, further validation is required before such biomarkers can be integrated into clinical diagnostics or used for therapeutic targeting.
Newsletters
Receive the latest pathologist news, personalities, education, and career development – weekly to your inbox.
