Usefulness of the Vitreous Fluid Analysis in the Translational Research of Diabetic Retinopathy

Abstract

Diabetic retinopathy (DR) is the major cause of acquired blindness in working-age adults. Current treatments for DR (laser photocoagulation, intravitreal corticosteroids, intravitreal antivascular endothelial growth factor (VEGF) agents, and vitreo-retinal surgery) are applicable only at advanced stages of the disease and are associated with significant adverse effects. Therefore, new pharmacological treatments for the early stages of the disease are needed. Vitreous fluid obtained from diabetic patients undergoing vitreoretinal surgery is currently used to explore the events that are taking place in the retina for clinical research. However, several confounding factors such as vitreous haemorrhage and concentration of vitreous proteins should be considered in the analysis of the results. In this paper we will focus on the vitreous fluid as a tool for exploring the mediators of DR and in particular the molecules related to inflammatory pathways. In addition, their role in the pathogenesis of DR will be discussed. The usefulness of new technologies such as flow cytometry and proteomics in identifying new candidates involved in the inflammatory process that occurs in DR will be overviewed. Finally, a more personalized treatment based on vitreous fluid analysis aiming to reduce the burden associated with DR is suggested.

Biomarkers in Diabetic Retinopathy

“…Pro-inflammatory factors, such as cytokines and chemokines, are shown in Table 6. They have been identified at increased levels in the retina and/or in the vitreous fluid [203,222]. Whilst the level of inflammation in diabetic retinopathy is often regarded as low, the levels for some inflammatory factors have been found to be quite high; for example, IL-8 levels in vitreous fluid were comparable to that found in pleural effusions of patients with pneumonia [223].…”

Proliferative Diabetic Retinopathy: An Overview of Vitreous Immune and Biomarkers

“…Diabetic retinopathy is often classified based on its severity into mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy (PDR) [1][2][3]. The major risk factors for developing DR are the duration of diabetes, hyperglycemia, hypertension, and dyslipidemia [4].…”

“…Several types of evidence prove the benefits of tight glycemic and blood pressure control in decelerating the progression of DR. Nevertheless, the numbers of DR patients and the development of DR complications are still increasing, while therapeutic approaches are limited [1,2].…”

“…The biochemical mechanisms implicated in DR progression have been shown in various animal models and patients with diabetes [1]. It is believed that the involvement of hyperglycemia and hormonal factors in diabetic patients could disturb hemostasis in the retina and change the balance of some mediators including growth factors, cytokines, inflammatory, and adhesion molecules [5].…”

“…These changes result in altered capillary permeability, apoptosis of capillary cells, and angiogenesis, leading to DR complications [3]. With improved clarity of molecular pathways in DR pathophysiology, the advancement of selective therapeutic approaches could be discovered and the management of DR could be more effective [1,5]. This chapter focuses on the inflammatory molecules and biomarkers involved in the pathophysiology of DR.…”