Abstract
Purpose:
To quantify expression of potential biomarkers of neoangiogenesis in the tears obtained from patients affected with corneal neovascularization (CNV) and to compare them with healthy, age-matched controls.
Methods:
Tears were collected by minisponge application from 19 eyes of 14 patients with CNV (average age: 52 years) and from 19 eyes of 16 healthy controls (average age: 48 years). Concentrations of Substance P (SP), Angiopoietin 2 (ANG2), VEGF-A and IL-1β in the tear samples were analyzed using a multiplex bead-based assays (Luminex Technology).
Results:
No differences were observed between all CNV patients and all controls for the 4 analyzed biomarkers. When gender was taken into consideration, there was a significant difference (P<0.05) only for ANG2 in the CNV group and for VEGF-A in both groups (higher levels in males). Gender was not associated with any significant differences (patients vs. controls) for any of the biomarkers considered.<br /> Although the two groups did not differ by age, SP was inversely related with age in controls (P<0.05), while IL1β, ANG2 and VEGF-A were positively correlated with age (P<0.05, P<0.001 and P<0.001, respectively). In the CNV group no correlations were observed between these biomarkers and age.<br /> ANG2 was positively correlated with VEGF-A and IL1β (P<0.01) in both groups. VEGF-A and IL1 β positively correlated with each other (P<0.05) in both groups. No correlation was found for SP vs. other biomarkers, except for VEGF-A in the control group (P<0.05).<br /> When ocular cicatricial pemphigoid (OCP) patients were extrapolated from the CNV group (N=6), a significant increase (P<0.01) in SP concentration together with a reduction (P<0.05) in VEGF-A level was observed in comparison to CNV non-OCP patients.<br /> CNV (clinically measured in quadrants) positively correlated with SP (P<0.01) and negatively with ANG2 (P<0.05). Inflamed eyes had higher values of these biomarkers (significance reached for IL1β).
Conclusions:
ANG2, VEGF-A and IL-1β show a similar expression pattern in tears, which is different from SP. Tear levels of these biomarkers are related with age and some of them to gender or specific disease (OCP).<br /> Finally, the expression levels of SP and ANG2 in the tear fluid are related to CNV severity, thus suggesting that these molecules may represent potential biomarkers to quantify CNV severity, and/or effective therapeutic targets.