Impact of Chronic Kidney Disease on Corneal Neuroimmune Features in Type 2 Diabetes

Abstract

Aim: To determine the impact of chronic kidney disease on corneal nerve measures and dendritic cell counts in type 2 diabetes. Methods: In vivo corneal confocal microscopy images were used to estimate corneal nerve parameters and compared in people with type 2 diabetes with chronic kidney disease (T2DM-CKD) (n = 29) and those with type 2 diabetes without chronic kidney disease (T2DM-no CKD) (n = 29), along with 30 healthy controls. Corneal dendritic cell densities were compared between people with T2DM-CKD and those with T2DM-no CKD. The groups were matched for neuropathy status. Results: There was a significant difference in corneal nerve fiber density (p < 0.01) and corneal nerve fiber length (p = 0.04) between T2DM-CKD and T2DM-no CKD groups. The two diabetes groups had reduced corneal nerve parameters compared to healthy controls (all parameters: p < 0.01). Immature central dendritic cell density was significantly higher in the T2DM-CKD group compared to the T2DM-no CKD group ((7.0 (3.8–12.8) and 3.5 (1.4–13.4) cells/mm2, respectively, p < 0.05). Likewise, central mature dendritic cell density was significantly higher in the T2DM-CKD group compared to the T2DM-no CKD group (0.8 (0.4–2.2) and 0.4 (0.6–1.1) cells/mm2, respectively, p = 0.02). Additionally, total central dendritic cell density was increased in the T2DM-CKD group compared to T2DM-no CKD group (10.4 (4.3–16.1) and 3.9 (2.1–21.0) cells/mm2, respectively, p = 0.03). Conclusion: The study showed that central corneal dendritic cell density is increased in T2DM-CKD compared to T2DM-no CKD, with groups matched for peripheral neuropathy severity. This is accompanied by a loss of central corneal nerve fibers. The findings raise the possibility of additional local factors exacerbating central corneal nerve injury in people with diabetic chronic kidney disease.

Chronic Kidney Disease Has No Impact on Tear Film Substance P Concentration in Type 2 Diabetes

“…The current study sought to ascertain whether changes in corneal nerve parameters are associated with an alteration in tear film substance P concentration in people with type 2 diabetes with concurrent chronic kidney disease compared to people with type 2 diabetes alone. Even though we demonstrated that corneal nerve parameters were reduced in type 2 diabetes with concurrent chronic kidney disease, consistent with previous findings [ 3 ], we found no difference in tear film substance P concentration between the two diabetes groups.…”

“…Recent studies have shown greater corneal nerve loss in diabetic chronic kidney disease compared to type 2 diabetes alone when the severity of peripheral neuropathy is matched between the two groups [ 3 ]. Tear film substance P is mainly expressed and released by corneal neurons and exerts its physiological effects through the neurokinin receptors on the ocular surface [ 4 , 5 ].…”

“…Tear film substance P is mainly expressed and released by corneal neurons and exerts its physiological effects through the neurokinin receptors on the ocular surface [ 4 , 5 ]. Hence, the idea or hypothesis explored in the present study is that loss of corneal nerve fibers because of diabetic chronic kidney disease [ 3 ] may be associated with an alteration in the concentrations of substance P in tears. Measuring tear film neuropeptides such as substance P concentration may assist in detecting subclinical neuropathy in diabetic chronic kidney disease.…”

“…Owing to the greater corneal neuropathy occurring in diabetic chronic kidney disease compared to type 2 diabetes alone [ 3 ], as well as the potential role of substance P in kidney function [ 11 , 12 ], we postulate that there may be differences in the tear film substance P concentration between individuals with type 2 diabetes with chronic kidney disease compared those with only type 2 diabetes.…”

PET Imaging for The Early Evaluation of Ocular Inflammation in Diabetic Rats by Using [ 18 F]-DPA-714

“…DM presents as a low-grade chronic in ammatory pathology. In ammation plays a pivotal role in the development and progression of diabetic eye disease (DED), in conjunction with increases in proin ammatory mediators, apoptosis, and vascular permeability (Asiedu et al 2022;Liu et al 2023). Current research on the link between in ammation and DED has focused on DR and DME.…”