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.

Figure 1

Main proinflammatory cytokines/chemokines increased in the vitreous fluid of diabetic patients (see text for details). Most of them participate also in the angiogenic process, which is essential for developing PDR. Anti-inflammatory/antiangiogenic cytokines also exist in the vitreous fluid of diabetic patients, but their concentration is not sufficient to counterbalance the inflammatory/angiogenic effect of proinflammatory cytokines.

Figure 2

Results obtained by using the fluorescence-based difference gel electrophoresis (DIGE) strategy showing the higher abundance of hemopexin in the vitreous fluid of diabetic patients with DME in comparison with Nondiabetic controls and PDR patients. (a) Three-dimensional images of the hemopexin spot corresponding to the image of a control (C), DME, and PDR samples. (b) Standardised abundance plot for hemopexin displaying the log of abundance observed for the spot in each of the four gel images corresponding to control (C), DME, and PDR samples. The line links the average abundance values for each group of samples (crosses). Student's t test results in a significant increase (P < 0.05) in DME sample in comparison with either C or PDR sample.