TGF-β Serum Levels in Diabetic Retinopathy Patients and the Role of Anti-VEGF Therapy.

Vincenza Bonfiglio,Claudio Bucolo,Matteo Fallico,Andrea Russo,Filippo Drago,Francesca Lazzara,Teresio Avitabile,Antonio Longo,Francesco Pignatelli,Michele Reibaldi,Federica Conti,Elina Ortisi,Corrado Pizzo,Chiara Bianca Maria Platania

doi:10.3390/ijms21249558

Abstract

Transforming growth factor β1 (TGFβ1) is a proinflammatory cytokine that has been implicated in the pathogenesis of diabetic retinopathy (DR), particularly in the late phase of disease. The aim of the present study was to validate serum TGFβ1 as a diagnostic and prognostic biomarker of DR stages. Thirty-eight subjects were enrolled and, after diagnosis and evaluation of inclusion and exclusion criteria, were assigned to six groups: (1) healthy age-matched control, (2) diabetic without DR, (3) non-proliferative diabetic retinopathy (NPDR) naïve to treatment, (4) NPDR treated with intravitreal (IVT) aflibercept, (5) proliferative diabetic retinopathy (PDR) naïve to treatment and (6) PDR treated with IVT aflibercept. Serum levels of vascular endothelial growth factor A (VEGF-A), placental growth factor (PlGF) and TGFβ1 were measured by means of enzyme-linked immunosorbent assay (ELISA). Foveal macular thickness (FMT) in enrolled subjects was evaluated by means of structural-optical coherence tomography (S-OCT). VEGF-A serum levels decreased in NPDR and PDR patients treated with aflibercept, compared to naïve DR patients. PlGF serum levels were modulated only in aflibercept-treated NPDR patients. Particularly, TGFβ1 serum levels were predictive of disease progression from NPDR to PDR. A Multivariate ANOVA analysis (M-ANOVA) was also carried out to assess the effects of fixed factors on glycated hemoglobin (HbA1c) levels, TGFβ1, and diabetes duration. In conclusion, our data have strengthened the hypothesis that TGFβ1 would be a biomarker and pharmacological target of diabetic retinopathy.

Highlights

Diabetic retinopathy (DR) is a complication of diabetes mellitus, and it is generally defined as the microvascular retinal complication of diabetes [1,2]
Duration of diabetes, poor glycemic control and lack of timely/appropriate treatment are the major causes of irreversible vision loss for DR patients [32]
We hereby investigated in a pilot study the clinical outcome (FMT by OCT) and serum cytokines levels (VEGFA, placental growth factor (PlGF) and Transforming growth factor β1 (TGFβ1)) in six groups of enrolled subjects: healthy controls, diabetic without signs of DR, naïve and aflibercept-treated non-proliferative diabetic retinopathy (NPDR), naïve and aflibercept-treated proliferative diabetic retinopathy (PDR) patients

Summary

Introduction

Diabetic retinopathy (DR) is a complication of diabetes mellitus, and it is generally defined as the microvascular retinal complication of diabetes [1,2]. Several substages have been identified in NPDR patients: early, moderate and severe NPDR. The latter is characterized by pervasive retinal hemorrhages and microvascular anomalies [3]. Diabetic macular edema (DME) is a main microvascular complication of PDR, it can occur in severe NPDR [5]. Current DR therapeutical approaches include intravitreal steroids [7] and anti-vascular endothelial growth factor (VEGF) agents, which are generally considered the first-line treatment [8]

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