Characterization of the vitreous proteome in diabetes without diabetic retinopathy and diabetes with proliferative diabetic retinopathy.
An understanding of the diabetes-induced alterations in vitreous protein composition in the absence and in the presence of proliferative diabetic retinopathy (PDR) may provide insights into factors and mechanisms responsible for this disease. We have performed a comprehensive proteomic analysis and comparison of vitreous samples from individuals with diabetes but without diabetic retinopathy (noDR) or with PDR and nondiabetic individuals (NDM). Using preparative one-dimensional SDS-PAGE and nano-LC/MS/MS of 17 independent vitreous samples, we identified 252 proteins from human vitreous. Fifty-six proteins were differentially abundant in noDR and PDR vitreous compared with NDM vitreous, including 32 proteins increased and 10 proteins decreased in PDR vitreous compared with NDM vitreous. Comparison of noDR and PDR groups revealed increased levels of angiotensinogen and decreased levels of calsyntenin-1, interphotoreceptor retinoid-binding protein, and neuroserpin in PDR vitreous. Biological pathway analysis revealed that vitreous contains 30 proteins associated with the kallikrein-kinin, coagulation, and complement systems. Five of them (complement C3, complement factor I, prothrombin, alpha-1-antitrypsin, and antithrombin III) were increased in PDR vitreous compared with NDM vitreous. Factor XII was detected in PDR vitreous but not observed in either NDM or noDR vitreous. PDR vitreous also had increased levels of peroxiredoxin-1 and decreased levels of extracellular superoxide dismutase, compared with noDR or NDM vitreous. These data provide an in depth analysis of the human vitreous proteome and reveal protein alterations that are associated with PDR.
Gao
Ben-Bo
BB
Research Division, Beetham Eye Institute, Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02215, USA.
Chen
Xiaohong
X
Timothy
Nigel
N
Aiello
Lloyd Paul
LP
Feener
Edward P
EP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism; D019295:Computational Biology; D003920:Diabetes Mellitus / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000378:metabolism; D005136:Eye Proteins / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000032:analysis / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D053719:Tandem Mass Spectrometry; D014821:Vitrectomy; D014822:Vitreous Body / Q000737:chemistry / Q000378:metabolism*
D001798:Blood Proteins; D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; D020543:Proteome