Abstract
Purpose:
Elevated levels of inflammatory cytokines and angiogenic factors are known in the vitreous of proliferative diabetic retinopathy (PDR). Recently, increase of circulating Th17 cells and elevated activation of Th17 signature genes have been reported in type 2 diabetic patients as well as the involvement of Th17 cells in development of type 1 diabetes. The study was conducted to investigate Th17-mediated immune responses involved in PDR by analysis of cytokine levels in the vitreous.
Methods:
Vitreous samples were collected from 9 eyes with epiretinal membrane, 7 eyes with macular hole, 5 eyes with retinal detachment, and 35 eyes with proliferative diabetic retinopathy undergoing vitrectomy for medical treatment from April 2012 to November 2013. Vitreous levels of 15 cytokines, IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, soluble CD40L, TNFα, and IFN-γ, were measured by using multiplex bead analysis.
Results:
IL-4, IL-6, IL-17A, IL-21, IL-22, IL-33, IL-33, soluble CD40L (sCD40L), IFN-γ, and TNFα were detected in the vitreous humor both of eyes with PDR and of eyes with non-diabetic retinopathy (non-DMR). However, all of these cytokines levels were higher in eyes with PDR (36.1 ± 5.46, 732.0 ± 193.9, 51.07 ± 6.67, 108.9 ± 26.7, 42.85 ± 9.28, 3.42 ± 2.15, 35.71 ± 8.57, 3.32 ± 1.69, and 20.56 ± 2.27, respectively) than eyes with non-DMR (14.37 ± 7.05, 462.7 ± 250.3, 10.72 ± 8.61, 27.02 ± 34.4, 11.41 ± 12.0, 1.63 ± 2.74, 7.15 ± 11.1, 0.74 ± 2.18 and 7.30 ± 2.93, respectively), in which there were significant differences in vitreous levels of IL-4, IL-17A, IL-22, sCD40L, and TNFα between them.
Conclusions:
The present study demonstrated that Th17 cell-mediated immune responses were involved in the development of proliferative diabetic retinopathy, suggesting that activated Th17 cells might play a pivotal role in the progression.