Abstract
BackgroundPreoperative treatment of anti-vascular endothelial growth factor (VEGF) agents is extensively used in proliferative diabetic retinopathy (PDR), but the molecular mechanism is not fully understood. The objective of this research is to observe change of protein profile induced by ranibizumab (an anti-VEGF agent) in vitreous humor from PDR patients and reveal the effects of anti-VEGF treatment on PDR.MethodsA proteomic method was used to identify differentially expressed proteins in vitreous humor. Untreated PDR patients were defined as PDR group, while those who treated with intravitreal injection of ranibizumab (IVR) were defined as IVR. Gene Ontology (GO) annotation and REACTOME pathways were obtained from DAVID Bioinformatics Resources. Intravitreal level of apolipoprotein C-I (APOC1), serpin peptidase inhibitor clade A member 5 (SERPINA5), tissue inhibitor of metalloproteinases (TIMP2), and keratin 1 (KRT1) were determined by enzyme-linked immuno sorbent assay (ELISA).Results339 differentially expressed proteins were identified in response to IVR. The most notable GO annotation describes the altered proteins was “innate immune response”. The most notable REACTOME pathway was “platelet degranulation”. ELISA result showed increased level of APOC1, SERPINA5, KRT1 and a decreased level of TIMP2 in PDR group compared with IVR.ConclusionsIn addition to decreasing VEGF level, ranibizumab is associated with change of human vitreous protein profile in patients with PDR, in which the differential proteins are involved in immune response, platelet degranulation, complement activation etc., suggesting that the effects of VEGF are involved in these signaling pathways.
Highlights
Preoperative treatment of anti-vascular endothelial growth factor (VEGF) agents is extensively used in proliferative diabetic retinopathy (PDR), but the molecular mechanism is not fully understood
Our results provided new findings:(1) 339 differentially expressed proteins were identified in vitreous humor from PDR patients in response to intravitreal injection of ranibizumab (IVR); (2) IVR treatment decrease intravitreal level of VEGF in PDR patients, and proteins regulating inflammation, apoptosis, angiogenesis, immune, bleeding and coagulation et al.; (3) apolipoprotein C-I (APOC1), tissue inhibitor of metalloproteinases (TIMP2), keratin 1 (KRT1) and SERPINA5 may be involved in the development of PDR and in the mechanism of the effects of anti-VEGF treatment
Total twenty-six patients were recruited in our study, including 8 untreated PDR patients, 9 PDR patients treated with IVR and 9 non-diabetic patients
Summary
Preoperative treatment of anti-vascular endothelial growth factor (VEGF) agents is extensively used in proliferative diabetic retinopathy (PDR), but the molecular mechanism is not fully understood. To better understand the pathophysiology of PDR and to identify DR-associated risk factors, a proteomics analysis was performed to compare vitreous protein profiles of DM patients with and without development of DR, and some studies results showed that many specific subset of proteins such as inflammation, complement, and coagulation cascade proteins, protease inhibitors, apolipoproteins, immunoglobulins, and cellular adhesion molecules are involved in the pathogenesis of DR [14,15,16,17]. Our results provided new findings:(1) 339 differentially expressed proteins were identified in vitreous humor from PDR patients in response to IVR; (2) IVR treatment decrease intravitreal level of VEGF in PDR patients, and proteins regulating inflammation, apoptosis, angiogenesis, immune, bleeding and coagulation et al.; (3) APOC1, TIMP2, KRT1 and SERPINA5 may be involved in the development of PDR and in the mechanism of the effects of anti-VEGF treatment
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