Proteomics and metabonomics of the Vitreous fluid as a new approach to identify new candidates in the pathogenesis of diabetic retinopathy

© 2012 Nova Science Publishers, Inc. All rights reserved. Diabetic retinopathy remains a leading cause of blindness and visual impairment among adults aged < 40 years in the developed world. Investigation into the processes involved in DR and the testing of new therapies are limited because the unavailability of human retina samples and the lack of diabetic animal models that faithfully replicates the features of human DR. Vitreous fluid obtained from diabetic patients undergoing vitreoretinal surgery is currently used as a surrogate for the retina in clinical research. However, the volume of vitreous fluid obtained after vitrectomy is approximately 1 ml and, therefore, only a few peptides or metabolites can be analyzed simultaneously. The recent development of high-throughput techniques such as proteomics and metabonomics has made it feasible to analyze both the protein and metabolite profiles in a massive manner. In recent years we have been able to demonstrate by proteomic analysis that several proteins such as complement factors (C3, C4b, C9 and factor B), Apo A1 and Apo-H were higher in the vitreous fluid from patients with proliferative DR (PDR) than non-diabetic patients, whereas the interstitial retinol-binding protein (IRBP) was lower. In addition, mRNA levels in the retina run in parallel with proteins, thus suggesting that the intraocular production of these proteins participates in the physiopathology of DR. Furthermore we have recently identified by proteomic analysis genuine proteins (ie. hemopexin and clusterin) differently expressed in the vitreous fluid from patients with diabetic macular edema. Finally, by using metabonomics we have been able to shown that, apart from a higher abundance of both lactate and glucose, significant deficits of galactitiol and ascorbic acid also exist in the vitreous fluid from PDR patients. The potential role of all these candidates in the pathogenesis of DR will be discussed in this chapter. In summary, proteomics and metabonomics of the vitreous fluid are useful not only for identifying potential candidates in the development of DR, but also for designing new approaches leading to a more efficient pharmacologic treatment of this devastating complication of diabetes.