Abstract
Purpose :
Retinal inflammation plays a major role in development and progression of Diabetic Retinopathy (DR) and Diabetic Macular Edema (DME). However, the impact of systemic inflammation and perturbations in immune cells in the pathogenesis of DR and DME in human diabetic subjects remains poorly characterized. Herein, we characterize the peripheral blood immune landscape in a large cohort of human subjects with Type 1 Diabetes (T1D) and Types 2 Diabetes (T2D) and varying degrees of DR and DME.
Methods :
Peripheral blood (5mL) of T1D (n=51), T2D (n=71), and nondiabetic (n=69) human subjects was collected according to standard procedures at the University of Alabama at Birmingham (UAB) Callahan Eye Hospital. From each subject, 200μL of whole blood was processed for flow cytometric assessment of peripheral immune cells using a BD FACS Celesta flow analyzer and analyzed using BD FlowJo software.
Results :
Individuals with T1D and T2D exhibited increased neutrophil-to-lymphocyte ratio (NLR) compared to patients without diabetes (p=0.035 and p=0.048 respectively). However, only patients with T2D+DR, specifically Non-Proliferative DR (NPDR), had an increased NLR as compared to T2D patients without DR (p=0.024). Individuals with T1D showed an increase in B cells when compared to patients without diabetes (p=0.043); in particular, plasma B cells, those responsible for antibody production, were increased in these individuals (p=0.018). Subjects with T2D+NPDR had an increase in B cells compared to those without DR (p=0.009). In individuals with T2D, the transitional B cell population was increased in individuals with Proliferative DR (PDR) (p=0.001), DR w/o DME (p= 0.038), and DR+DME (p=.007) as compared to patients without DR. Subjects with T2D+NPDR (p=0.029), PDR (p=0.036), and DR+DME (p=0.0001) exhibited an elevation of Th1 cells compared to individuals without DR. Th17, gut derived immune cells, were only elevated in T2D subjects with DR compared to those without DR (p=0.011).
Conclusions :
T1D and T2D are associated with an increase in inflammatory cell subsets. Subjects with T2D and DR, but not those with T1D, exhibited increased granulocytes, B cells, and Th1 cells suggesting a potential interplay between myeloid and lymphoid cells in the pathogenesis of DR in T2D. Circulating immune cells may represent unique biomarkers that can be followed overtime to identify not only the presence of DR and DME but also progression.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.