title: Enzyme-induced vitreolysis can alleviate the progression of diabetic retinopathy through the HIF-1α pathway.
abstract: OBJECTIVE
  We studied the mechanism by which complete posterior vitreous detachment by enzyme-induced vitreolysis alleviates the progression of diabetic retinopathy.
  
  
  METHODS
  We enrolled 50 diabetic rats and 20 normal control rats in this study. The right eyes of these diabetic rats were treated with a hyaluronidase (5 U) plus plasmin (0.25 U) by intravitreous injection (ET group), while the left eyes of diabetic rats (DR group) and eyes of the normal rats (NC group) were injected with balanced saline. Eight months after intravitreous injection, the oxygen concentration in the vitreous was measured, and the expression levels of hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), and basic fibroblast growth factor (bFGF) in retinas were determined by real-time PCR and Western blot. Clinical observation, visual electrophysiology tests, and scanning electron microscopy (SEM) also were performed on the rats.
  
  
  RESULTS
  SEM results showed that the surface of retinas in the ET group had little vitreous cortex and the inner limiting membrane could be observed. The oxygen concentration of the midvitreous was higher in the ET group than other groups. A significantly high expression of HIF-1α, VEGF, and bFGF was detected in the retinas of the DR group compared to the ET and NC groups. In visual electrophysiology tests, amplitude decline and peak time latency were found in diabetic rats, and changes in the DR group were more obvious than in the ET group.
  
  
  CONCLUSIONS
  Enzyme-induced vitreolysis can increase oxygen concentration in the vitreous, with reduced expression of HIF-1α, VEGF, and bFGF, and increased expression of PEDF in the retinas, thus alleviating the progression of diabetic retinopathy.
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Chuanyin
authors.initials: C
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Jingfa
authors.initials: J
authors.lastname: Zhang
authors.forename: Limei
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Huang
authors.forename: Yuting
authors.initials: Y
authors.lastname: Yao
authors.forename: Xin
authors.initials: X
authors.lastname: Che
authors.forename: Xianqun
authors.initials: X
authors.lastname: Fan
authors.forename: Shengfang
authors.initials: S
authors.lastname: Ge
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005341:Fibrinolysin / Q000008:administration & dosage; D005343:Fibrinolytic Agents / Q000008:administration & dosage; D005786:Gene Expression Regulation; D006821:Hyaluronoglucosaminidase / Q000008:administration & dosage*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000235:genetics*; D058449:Intravitreal Injections; D008297:Male; D008855:Microscopy, Electron, Scanning; D012313:RNA / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D014822:Vitreous Body / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D005343:Fibrinolytic Agents; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012313:RNA; D006821:Hyaluronoglucosaminidase; D005341:Fibrinolysin
keywords: HIF-1α; PEDF; VEGF; enzyme-induced vitreolysis; oxygen concentration; posterior vitreous detachment