Abstract

In this study, we compare the vitreous cytokine profile in patients with proliferative diabetic retinopathy (PDR) to that of patients without PDR. The identification of novel cytokines involved in the pathogenesis of PDR provides candidate therapeutic targets that may stand alone or work synergistically with current therapies in the management of diabetic retinopathy. Undiluted vitreous humor specimens were collected from 74 patients undergoing vitrectomy for various vitreoretinal disorders. Quantitative immunoassay was performed for a panel of 36 neuroinflammatory cytokines in each specimen and assessed to identify differences between PDR (n = 35) and non-PDR (n = 39) patients. Levels of interleukin-8 (IL-8), IL-15, IL-16, vascular endothelial growth factor (VEGF), VEGF-D, c-reactive protein (CRP), serum amyloid-A (SAA), and intracellular adhesion molecule-1 (ICAM1) were significantly increased in the vitreous of PDR patients compared to non-PDR patients (p < 0.05). We report novel increases in IL-15 and IL-16, in addition to the expected VEGF, in the human vitreous humor of patients with PDR. Additionally, we confirm the elevation of ICAM-1, VCAM-1, SAA, IL-8 and CRP in the vitreous of patients with PDR, which has previously been described.

Highlights

  • Diabetic retinopathy (DR) is the leading cause of visual impairment among working age adults in the United States (US) [1]

  • Patients with Proliferative diabetic retinopathy (PDR), diabetic patients with mild, moderate and severe non-proliferative diabetic retinopathy, and those without a diagnosis of diabetes were included in this study

  • Of the 39 in the control group without PDR, 31 patients were nondiabetic while 8 were diabetic patients who had either no retinopathy or retinopathy that was less than proliferative

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Summary

Introduction

Diabetic retinopathy (DR) is the leading cause of visual impairment among working age adults in the United States (US) [1]. Proliferative diabetic retinopathy (PDR), which is the most advanced stage of diabetic retinopathy, can be associated with severe visual impairment and blindness. It is characterized by retinal ischemia and an ischemia-induced upregulation of angiogenic factors, namely, vascular endothelial growth factor (VEGF) [1,4]. Multiple studies have demonstrated that along with pro-angiogenic factors, patients with PDR have elevated intraocular concentrations of inflammatory cytokines [6,7,8], raising the possibility that additional therapeutic avenues exist, beyond targeting VEGF, for the treatment of PDR.

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