title: Succinate increases in the vitreous fluid of patients with active proliferative diabetic retinopathy.
abstract: OBJECTIVE
  To examine vitreous succinate levels from proliferative diabetic retinopathy (PDR) patients and ascertain their association with PDR activity.
  
  
  METHODS
  Comparative case series.
  
  
  METHODS
  A total of 81 eyes of 72 PDR patients were divided into active PDR (22 eyes), quiescent PDR (21 eyes), and active PDR with intravitreal bevacizumab injection (38 eyes). Twenty epiretinal membrane (ERM) patients (21 eyes) served as controls.
  
  
  RESULTS
  Mean vitreous succinate levels were 1.27 μM in ERM and 2.20 μM in PDR, with the differences statistically significant (P = .03). When comparing mean vitreous succinate levels (active PDR: 3.32 μM; quiescent PDR: 1.02 μM; active PDR with intravitreal bevacizumab injection: 1.20 μM), significant differences were found between active and quiescent PDR (P < .01) and between active PDR and active PDR with intravitreal bevacizumab injection (P < .01). Even though succinate levels were low, retinopathy activities were very high in patients with active PDR with intravitreal bevacizumab injection. Mean vitreous vascular endothelial growth factor (VEGF) levels (active PDR: 1696 pg/mL; quiescent PDR: 110 pg/mL; active PDR with intravitreal bevacizumab injection: n.d.) were similar to previous reports. Mean vitreous erythropoietin levels (active PDR: 703 mIU/mL; quiescent PDR: 305 mIU/mL; active PDR with intravitreal bevacizumab injection: 1562 mIU/mL) suggested very high retinopathy activities in patients with active PDR with intravitreal bevacizumab injection.
  
  
  CONCLUSIONS
  Succinate, like VEGF, may be an angiogenic factor that is induced by ischemia in PDR. Although succinate is reported to promote VEGF expression, VEGF inhibition decreases succinate. Thus, VEGF, via a positive feedback mechanism, may regulate succinate.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Suzuma
authors.forename: Toshihide
authors.initials: T
authors.lastname: Maki
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kinoshita
authors.forename: Eiko
authors.initials: E
authors.lastname: Tsuiki
authors.forename: Azusa
authors.initials: A
authors.lastname: Fujikawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitaoka
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D001082:Aqueous Humor / Q000378:metabolism; D000068258:Bevacizumab; D002851:Chromatography, High Pressure Liquid; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000378:metabolism*; D019773:Epiretinal Membrane / Q000378:metabolism; D004921:Erythropoietin / Q000378:metabolism; D005260:Female; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D015861:Retinal Neovascularization / Q000378:metabolism; D019802:Succinic Acid / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; D000068258:Bevacizumab; D019802:Succinic Acid