Abstract
Purpose :
Pericyte dropout is an early pathologic hallmark of diabetic retinopathy (DR) and may contribute to vascular instability and disease progression. Aqueous humor (AH) and vitreous humor (VH) biomarkers reflecting pericyte status within the retina may therefore be prognostic for progression to more severe, vision-threatening forms of DR, including proliferative DR (PDR) and diabetic macular edema (DME) and may help guide treatment decisions. In this study, putative pericyte-selective markers were evaluated in AH, VH, and plasma for their ability to reflect DR severity.
Methods :
AH, VH, and plasma specimens (n=181) were collected during ocular surgery or injection procedures from the study population (n=98) spanning nondiabetic, diabetes mellitus without DR (DM), non-proliferative DR without DME (NPDR), PDR without DME, and DME patients. 24 patients from the total study population had matched VH, AH and plasma. Concentrations of Regulator of G-protein signaling 5 (RGS5), Pigment epithelium-derived factor (PEDF), and Pyruvate dehydrogenase kinase isozyme 4 (PDK4) were measured in samples via enzyme-linked immunosorbent assay. Kruskal-Wallis ANOVA test was used to compare biomarker levels across cohorts, Dunn’s multiple comparison test was used for pairwise comparison to DM population, and a Spearman correlation evaluated the relationship between matrices.
Results :
In VH, RGS5 was significantly increased in PDR and DME cohorts relative to DM (p=0.0019, p=0.0253 respectively), PEDF was significantly increased in PDR and DME cohorts (p=0.0004, p=0.0157 respectively), and PDK4 was significantly increased in the PDR cohort (p=0.0271). RGS5, PEDF, and PDK4 demonstrated significant correlation between matched AH and VH samples (r=0.8798 p=<0.0001, r=0.6650 p=0.0005, and r=0.5774 p=0.002 respectively). AH had similar significant elevations in advanced disease cohorts over DM for RGS5 and PDK4. None of the markers showed statistically significant elevations over the DM population in plasma across the DR cohorts.
Conclusions :
These preliminary results demonstrate that multiple pericyte-selective biomarkers change with disease severity in diabetic retinopathy. This change with disease progression supports further investigation into their utility as prognostic biomarkers.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.