Age-related macular degeneration (AMD) often has subtle disease onset with few noticeable symptoms, making early detection key. A recent study investigated inflammasome signaling proteins, prominent biomarkers in the central nervous system, as potential biomarkers for AMD and found that certain elevated protein levels may increase the odds of an AMD diagnosis.
“The most definitive risk factor for AMD is aging, with smoking and hypertension as possible contributors, among others,” the researchers said. The inflammatory response related to aging, known as ‘inflammaging,’ has been associated with early stages of neurodegeneration and is involved with the inflammasome, a multiprotein complex of the innate immune response.
“The activation of the inflammasome protein caspase-1, in association with apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), triggers a cascade of molecular events that promote the release of the proinflammatory cytokines interleukin (IL)-1β and IL-18,” they wrote in their paper. Because AMD is related to aging, the researchers stated that it’s important to identify blood biomarkers that can provide systemic data for AMD diagnoses.
The researchers analyzed serum from healthy controls and AMD patients for protein levels of ASC, IL-18 and C-reactive protein (CRP) to determine cutoff points, positive and negative predictive values and ROCs. They found that all three levels were elevated in the serum of AMD patients compared with healthy controls.
IL-18 levels demonstrated a statistically significant linear correlation with ASC, suggesting that 19% of IL-18 could be explained by ASC protein levels in serum, the researchers noted. “Moreover,” they added, “a logistic regression model for the diagnosis of AMD consists of ASC and having a diagnosis of hypertension, indicating that these two factors (elevated levels of ASC and a diagnosis of hypertension) are associated with the diagnosis of AMD.”
The researchers concluded that ASC and IL-18 contribute to AMD pathology and are good candidates as inflammatory biomarkers. “We suggest that ASC and IL-18 can be used as part of a platform of biomarkers that in conjunction with other proteins can be used to better diagnose and prognose AMD since here we show that ASC and IL-18 are associated with the diagnosis of AMD.”
Weaver C, Cyr B, de Rivero Vaccari JC, et al. Inflammasome proteins as inflammatory biomarkers of age-related macular degeneration. Transl Vis Sci Technol 2020;9:13:27.