title: Evaluation of vitreous levels of advanced glycation end products and angiogenic factors as biomarkers for severity of diabetic retinopathy.
abstract: OBJECTIVE
  Glyceraldehyde-derived advanced glycation end products (glycer-AGE; also called Toxic-AGE [TAGE]) play a crucial role in the pathogenesis of diabetic angiopathy. However, the relationships between vitreous glycer-AGE levels and diabetic retinopathy (DR) severity, and between glycer-AGE levels and the levels of other angiogenic factors remain unknown. We investigated the correlation between levels of vitreous biomarkers, including glycer-AGE and angiogenic factors (vascular endothelial growth factor [VEGF], interleukin [IL]-8, leptin, placental growth factor [PlGF], endoglin, and fibroblast growth factor [FGF]-2) in patients with DR, using three DR staging groups.
  
  
  METHODS
  In this cross-sectional study, we examined 33 eyes from 33 patients with diabetes mellitus who underwent a vitrectomy (non-proliferative DR [NPDR, n = 8]; PDR with simple vitreous haemorrhage [VH, n = 17]; or PDR with a fibrovascular proliferative membrane [FVM, n = 8]). Vitreous levels of glycer-AGE and VEGF were evaluated using enzyme-linked immunosorbent assays. Vitreous levels of IL-8, leptin, PlGF, endoglin, and FGF-2 were evaluated using beaded assay methods.
  
  
  RESULTS
  Vitreous levels of glycer-AGE in the FVM group were significantly higher than those in the NPDR and VH groups (all p < 0.05). Vitreous levels of VEGF (r = 0.85, p = 1.7 × 10-6) and leptin (r = 0.60, p = 5.0 × 10-3) were significantly correlated with levels of PlGF.
  
  
  CONCLUSIONS
  The two systems (VEGF-PlGF-leptin and glycer-AGE) were represented in these measured biomarkers. High vitreous levels of both VEGF and glycer-AGE may be linked to more severe DR, suggesting that anti-VEGF and anti-TAGE therapy may be an important part of the therapeutic strategy for DR.
authors.affiliation: Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. makikokumakawa@gmail.com.
authors.forename: Makiko
authors.initials: M
authors.lastname: Katagiri
authors.affiliation: Division of Ophthalmology, Department of Visual Sciences, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Shoji
authors.affiliation: Division of Ophthalmology, Department of Visual Sciences, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Inada
authors.affiliation: Department of Ophthalmology, The University of Tokyo, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kato
authors.affiliation: Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Kitano
authors.affiliation: Department of Medicine, Diabetes Center, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Uchigata
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D003430:Cross-Sectional Studies; D003930:Diabetic Retinopathy / Q000378:metabolism*; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: D043925:Angiogenesis Inducing Agents; D015415:Biomarkers; D017127:Glycation End Products, Advanced; D036341:Intercellular Signaling Peptides and Proteins
keywords: Advanced glycation end products; Diabetic retinopathy; Leptin; Placental growth factor; Vascular endothelial growth factor; Vitreous fluid