Abstract
Purpose :
We and others previously reported that IL-17A plays a pivotal role in VEGF production, diabetic retinopathy, and retinal neovascularization. In cancer, anti-IL-17RA increases the efficacy of anti-VEGF treatments. We hypothesized that anti-IL-17RA would increase the efficacy of anti-VEGF treatment for diabetic macular edema.
Methods :
Blood of non-diabetics, Type II diabetics with diabetic macular edema that were categorized as non-responders and responders to anti-VEGF treatments was collected at Louis Stokes Cleveland VA Medical Center (n=25/group). Plasma and peripheral blood mononuclear cells (PBMC) were isolated, and protein lysates collected. Levels of IL-17A was quantified in PBMC protein lysates by ELISA. Plasma (200ml/well) was added to 10,000 human retinal endothelial cells (hREC) with or without anti-IL-17RA (IL-17A receptor antagonist) for 16h, cellular protein lysates were collected and normalized, for automated Western immunoblot analysis of vascular tight junction proteins of the retina; Zonula occludens (ZO)-1 and Vascular endothelial (VE)-Cadherin.
Results :
IL-17A was not detected in the PBMC of non-diabetics, and detected in all diabetics with macular edema. The level of IL-17A was significantly higher in the anti-VEGF non-responders than responders. Additionally, tight junction proteins ZO-1 and VE-Cadherin was significantly decreased in human retinal endothelial cells (hREC) that were incubated with plasma of diabetics with macular edema when compared to hREC incubated with plasma of non-diabetics. When hREC were treated with anti-VEGF prior to plasma incubation, ZO-1 and VE-Cadherin degradation was significantly decreased in hREC incubated with plasma of anti-VEGF responders but not in hREC incubated with plasma of anti-VEGF non-responders. However, when hREC were incubated with anti-IL-17RA prior to anti-VEGF, and incubated with plasma of nondiabetics or anti-VEGF non-responders, ZO-1 and VE-Cadherin degradation in the hREC incubated with plasma of anti-VEGF non-responders was very similar (not significantly different) than hREC incubated with plasma of non-diabetic controls.
Conclusions :
These results provide evidence that anti-IL-17RA enhances the efficacy of anti-VEGF treatment for diabetic macular edema. Further, our results suggest that anti-IL-17RA could be a good candidate therapeutic for diabetics with macular edema that do not respond to anti-VEGF treatment.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.