Parallel Systemic and Tissue-Specific Expression Pattern of Inflammatory Cytokines in Human Diabetic Retinopathy

Abstract

Purpose: : Chronic inflammatory processes are involved in the pathogenesis of diabetic retinopathy. The expression pattern of specific inflammatory factors could serve as biomarkers of disease progression. We have conducted studies in diabetic patients assessing the levels of several inflammatory cytokines including interleukin 17 (IL-17), interleukin 6 (IL-6) and interferon-related protein 10 (IP10) in relation to progression of DR. To determine whether systemic levels of inflammatory mediators could mirror retinal tissue specific alterations, we have also analyzed the expression pattern of these pro-inflammatory factors in post-mortem retinas of diabetic donors.

Methods: : One hundred seventy one diabetic patients (Type 1 and Type 2) were enrolled for the study and subjected to ophthalmological evaluation (EDTRS,Fluoroangiography). Sera from diabetic and non diabetic patients were subjected to MULTIPLEX ELISA assay to determine cytokines expression. Retinas from diabetic (n=11) and non diabetic donors (n=7) were obtained from Georgia Eye Bank and analyzed by ELISA, Western blotting and immunohistochemistry analyses.

Results: : Multiplex ELISA analysis revealed a significant increase in IL-6, IL-17 and IP-10 in serum of diabetic patients versus non diabetic patients (p<0.01). IL-17 levels were particularly increased in patients with macular edema and proliferative diabetic retinopathy, whereas levels of IP-10 and IL-6 were increased in all the DR population of patients. In the human post-mortem retina levels of IL-6, IL-17 and IP-10 were also elevated as well as the expression of their respective receptors.

Conclusions: : Systemic and tissue specific events are likely to play critical, but yet distinct roles, in sustaining the inflammatory processes associated with the induction and progression of diabetic retinopathy (DR). Ideal candidate as biomarker of disease should show similar activation/ expression pattern in peripheral and retinal tissue levels. The results of our study determined that the expression pattern of IL-6, IL-17 and IP-10 showed similar expression pattern in both systemic and retinal levels, thus warrant further clinical studies to validate these factors as biomarkers of disease.

Keywords: diabetic retinopathy • inflammation • cytokines/chemokines