CORNEAL DENDRITIC CELL DYNAMICS ARE ASSOCIATED WITH CLINICAL FACTORS IN TYPE 1 DIABETES

Abstract

Purpose : Immature dendritic cells (imDCs) have recently been reported to migrate at a speed of approximately 1 µm/min in the healthy human cornea, as seen with time-lapsed imaging using in vivo confocal microscopy (IVCM). Mature, immature, and putative sub-epithelial dendritic cell density (DCD) and imDC dynamics were explored in people with and without type 1 diabetes.

Methods : Twenty participants with type 1 diabetes (age 55 ± 11 years, duration of diabetes: 29 ± 14 years) from the LANDMark study (a 7-year, two-site, natural history study of type 1 diabetic participants) and 10 age- and gender-matched participants without diabetes (age 55 ± 17 years) underwent IVCM at the whorl region of the nerve plexus to quantify the density of immature, mature and putative dendritic cell phenotypes. Trajectory (length travelled/time) and displacement (distance from to and end points/time) speeds as well as persistence ratio (displacement/trajectory) were calculated from at least three imDCs per cornea. Blood biochemistry and metabolic measures from plasma (including hemoglobin A1C) and urine samples were retrospectively analysed.

Results : Mature DCD was higher in diabetic participants compared to controls (12 ± 13 vs 4 ± 4 cell/mm2, p=0.02). Other cell dynamics and DCD did not differ between groups. Significant associations were found between imDC density and high-density lipoprotein (HDL) cholesterol (mmol/L) (ρ=0.6; p=0.01) and triglycerides (mmol/L) (ρ=-0.6; p=0.01). Putative DCD correlated with HDL cholesterol (mmol/L) (ρ=-0.5; p=0.02). Average imDC trajectory path (µm/min) correlated with duration of diabetes (ρ=-0.5; p=0.03) and estimated glomerular filtration rate (eGFR) (mL/min) (ρ=0.5; p=0.03). Average imDC displacement associated with duration of diabetes (ρ=-0.5; p=0.03), eGFR (mL/min) (ρ=0.7; p<0.01). Average imDC persistence (ratio) correlated with eGFR (mL/min) (ρ=0.6; p=0.01).

Conclusions : This study suggests that metabolic parameters may be reflected in the cornea as observed by imDC dynamics using IVCM and provides evidence of the link between imDCs dynamics and lipid levels, renal function, and duration of type 1 diabetes.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.