Abstract
Purpose :
Interleukin (IL)-17A has been previously reported to play a role in the onset of diabetic retinopathy in diabetic mice. Yet it is unknown if IL-17A plays this same role in human diabetics. We hypothesized that diabetes induces IL-17A production in Type II diabetics, which enhances retinal pathology in diabetic retinopathy.
Methods :
Blood of Type II diabetics or non-diabetics (n=30/group) was collected, as well as vitreous of patients receiving a vitrectomy (n=3/group). Sera and peripheral blood mononuclear cells (PBMC) were isolated, and protein lysates collected. Levels of IL-17A was quantified in the PBMC protein lysates and vitreous by ELISA. Sera (400μl/well) was added to 10,000 human retinal endothelial cells with or without anti-IL-17RA (IL-17A receptor antagonist) for 16h, cellular protein lysates (n=5/group) were collected and normalized, for Western immunoblot analysis of tight junction proteins of the retinal vasculature; Vascular endothelial (VE)-Cadherin and Zonula occludens (ZO)-1.
Results :
Only negligible levels of IL-17A was detected in the PBMC’s of blood and vitreous of non-diabetic patients. While most of the diabetics without retinopathy had detectable levels of IL-17A, which was significantly increased (p<0.01) in patients with diabetic retinopathy. No IL-17A was detected in the vitreous of non-diabetic patients, yet ~15pg/ml of IL-17A was detected in the vitreous of patients with diabetic retinopathy. Additionally, IL-17A was significantly increased in anti-VEGF non-responders (patients receiving anti-VEGF treatment for proliferative diabetic retinopathy) than responders (n=10/group). Finally, tight junction proteins VE-Cadherin and ZO-1 was significantly decreased (p<0.01) in human retinal endothelial cells that were incubated with sera of diabetic retinopathy patients with high levels of IL-17A than non-diabetics. However, VE-Cadherin and ZO-1 degradation was significantly decreased (p<0.01) when IL-17A signaling was blocked in retinal endothelial cells by anti-IL-17RA antibody.
Conclusions :
These results support our hypothesis that diabetes induces IL-17A production in Type II diabetics, which enhances retinal pathology in diabetic retinopathy. Further ex vivo studies of vascular leakage and angiogenesis will be needed to define the role of IL-17A in the onset and progression of diabetic retinopathy in diabetics.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.