Background: Diabetic Retinopathy (DR), one of the major microvascular complications commonly occurring in diabetic patients, can be classified into Proliferative Diabetic Retinopathy (PDR) and Non-Proliferative Diabetic Retinopathy (NPDR). Currently, available therapies are only targeted for later stages of the disease in which some pathologic changes may be irreversible. Thus, there is a need to develop new treatment options for earlier stages of DR through revealing pathological mechanisms of PDR and NPDR.
Objective: The purpose of this study was to characterize the proteomes of diabetes through quantitative analysis of PDR and NPDR.
Methods: Vitreous body was collected from three groups: control (non-diabetes mellitus), NPDR, and PDR. Vitreous proteins were digested to peptide mixtures and analyzed using LC-MS/MS. MaxQuant was used to search against the database and statistical analyses were performed using Perseus. Gene ontology analysis, related-disease identification, and protein-protein interaction were performed using the differential expressed proteins.
Results: Twenty proteins were identified as critical in PDR and NPDR. The NPDR group showed different expressions of kininogen-1, serotransferrin, ribonuclease pancreatic, osteopontin, keratin type II cytoskeletal 2 epidermal, and transthyretin. Also, prothrombin, signal transducer and activator of transcription 4, hemoglobin subunit alpha, beta, and delta were particularly up-regulated proteins for PDR group. The up-regulated proteins related to complement and coagulate cascades. Statherin was down-regulated in PDR and NPDR compared with the control group. Transthyretin was the unique protein that increased its abundance in NPDR compared with the PDR and control group.
Conclusion: This study confirmed the different expressions of some proteins in PDR and NPDR. Additionally, we revealed uniquely expressed proteins of PDR and NPDR, which would be differential biomarkers: prothrombin, alpha-2-HS-glycoprotein, hemoglobin subunit alpha, beta, and transthyretin.
[http://dx.doi.org/10.2337/dc11-1909] [PMID: 22301125]
[http://dx.doi.org/10.1111/j.1755-3768.2012.02445.x] [PMID: 22682034]
[http://dx.doi.org/10.1021/acs.jproteome.5b00900] [PMID: 26490944]
[http://dx.doi.org/10.1016/j.jprot.2011.12.006] [PMID: 22200677]
[http://dx.doi.org/10.1001/archopht.126.8.1076] [PMID: 18695102]
[http://dx.doi.org/10.1167/iovs.18-24122] [PMID: 30025106]
[http://dx.doi.org/10.1016/j.clinbiochem.2011.10.006] [PMID: 22040812]
[http://dx.doi.org/10.1093/nar/gky1106] [PMID: 30395289]