Corneal Immune Cells and Their Relation to Diabetic Peripheral Neuropathy and Neuropathic Pain

As corneal dendritic cells (DCs) are immune cells that can reflect systemic inflammatory activity, this study aimed to investigate whether the density and maturity of corneal DCs are associated with diabetes, diabetic peripheral neuropathy (DPN), and neuropathic pain.

Participants included individuals with type 1 diabetes mellitus (T1DM) and painful DPN (n = 19), T1DM and painless DPN (n = 15), T1DM without DPN (n = 19), and healthy controls (n = 20). Corneal confocal microscopy was used to quantify and categorize DCs as either mature or immature and based on their proximity to corneal nerves.

No significant differences between groups were observed in total DC density (p = 0.34). Subgroup analysis revealed distinct patterns in which participants with DPN (regardless of pain status) exhibited a higher density of immature DCs distant from corneal nerves compared to those without DPN (14.4 [6.64-37.5] vs. 3.75 [0-17.7] no./mm², p < 0.05). Healthy controls had a greater density of immature DCs near the nerves compared to the T1DM + DPN group (2.8 [0-8.44] vs. 8.3 [3.12-15.1] no./mm²), while the T1DM + DPN group had a higher density than the painful DPN (3.1 [1.25-5.62] no./mm²). For mature DCs near the nerves, individuals with painful DPN (2.5 [1.4-3.12] no./mm²) had a lower density compared to all other groups.

This study demonstrates distinct patterns of corneal DC distribution in relation to painful and painless DPN. The findings suggest that immune-mediated mechanisms may play a role in the development of neuropathy and neuropathic pain in diabetes. The pathophysiological significance remains to be clarified.

ClinicalTrials.gov: NCT04078516.