title: Comparison of the effect of intravitreal bevacizumab and intravitreal fasudil on retinal VEGF, TNFα, and caspase 3 levels in an experimental diabetes model.
abstract: OBJECTIVE
  To evaluate the influence of an intravitreal injection of bevacizumab and fasudil on the retinal vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNFα), and caspase 3 levels in a diabetic rabbit model.
  
  
  METHODS
  The study included 6 healthy rabbits (Group 1), 6 rabbits with experimentally induced diabetes mellitus (DM) (Group 2), 7 rabbits with experimentally induced DM to which intravitreal bevacizumab was administered (Group 3), and 7 rabbits with experimentally induced DM to which intravitreal fasudil was administered (Group 4). An intravitreal injection of 1.25mg/50µL bevacizumab in the right eye of rabbits in Group 3 and an intravitreal injection of 0.0064mg/50µL fasudil in the right eye of rabbits in Group 4 were administered on day 21 after the induction of DM. The studied eyes of the rabbits were enucleated three days after the intravitreal injection. The TNFα, VEGF, and caspase 3 levels were determined using the ELISA method.
  
  
  RESULTS
  There was a statistically significant difference in the VEGF and caspase 3 levels between groups (P=0.005 and P =0.013, respectively), but the TNFα level did not differ significantly between groups (P=0.792). It was found that VEGF levels were significantly lower in Group 1 and Group 3 than in Group 2 using the Mann-Whitney U test with the Bonferroni correction (P=0.004 for both comparison). There was no statistically significant difference between other groups with regard to VEGF levels (the P value ranged between 0.015 and 0.886). Although the P values of the caspase 3 levels were 0.015 for Group 1 and Group 4, 0.038 for Group 2 and Group 3, and 0.018 for Group 3 and Group 4, these P values remained above the threshold P value of 0.0083, which was the statistically significant level for post hoc tests.
  
  
  CONCLUSIONS
  An intravitreal injection of bevacizumab decreased both the VEGF level, which plays a role in angiogenesis, and the caspase 3 level, which plays a role in apoptosis. Although not as effective as bevacizumab, fasudil had a beneficial effect on the VEGF levels but significantly increased the caspase 3 levels.
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Abant Izzet Baysal University, Bolu 14280, Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Celik
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Abant Izzet Baysal University, Bolu 14280, Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Ulaş
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Abant Izzet Baysal University, Bolu 14280, Turkey.
authors.forename: Zeynep Güneş
authors.initials: ZG
authors.lastname: Ozünal
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Abant Izzet Baysal University, Bolu 14280, Turkey.
authors.forename: Tülin
authors.initials: T
authors.lastname: Fırat
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Abant Izzet Baysal University, Bolu 14280, Turkey.
authors.forename: Serdal
authors.initials: S
authors.lastname: Celebi
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Abant Izzet Baysal University, Bolu 14280, Turkey.
authors.forename: Umit
authors.initials: U
authors.lastname: Doğan
keywords: bevacizumab; caspase 3; experimental diabetes; fasudil; tumor necrosis factor alpha; vascular endothelial growth factor