Quantitative Proteomics Analysis of Vitreous Humor from Diabetic Retinopathy Patients

Initial
triggers for diabetic retinopathy (DR) are hyperglycemia-induced
oxidative stress and advanced glycation end-products. The most pathological
structural changes occur in retinal microvasculature, but the overall
development of DR is multifactorial, with a complex interplay of microvascular,
neurodegenerative, genetic/epigenetic, immunological, and secondary
inflammation-related factors. Although several individual factors
and pathways have been associated with retinopathy, a systems level
understanding of the disease is lacking. To address this, we performed
mass spectrometry based label-free quantitative proteomics analysis
of 138 vitreous humor samples from patients with nonproliferative
DR or the more severe proliferative form of the disease. Additionally,
we analyzed samples from anti-VEGF (vascular endothelial growth factor)
(bevacizumab)-treated patients from both groups. In our study, we
identified 2482 and quantified the abundancy of 1351 vitreous proteins.
Of these, the abundancy of 230 proteins was significantly higher in
proliferative retinopathy compared with nonproliferative retinopathy.
This specific subset of proteins was linked to inflammation, complement,
and coagulation cascade proteins, protease inhibitors, apolipoproteins,
immunoglobulins, and cellular adhesion molecules, reflecting the multifactorial
nature of the disease. The identification of the key molecules of
the disease is critical for the development of new therapeutic molecules
and for the new use of existing drugs.