title: Effect of intravitreal injection of bevacizumab-chitosan nanoparticles on retina of diabetic rats.
abstract: OBJECTIVE
  To investigate the effects of intravitreal injection of bevacizumab-chitosan nanoparticles on pathological morphology of retina and the expression of vascular endothelial growth factor (VEGF) protein and VEGF mRNA in the retina of diabetic rats.
  
  
  METHODS
  Seventy-two 3-month aged diabetic rats were randomly divided into 3 groups, each containing 24 animals and 48 eyes. Both eyes of the rats in group A were injected into the vitreous at the pars plana with 3µL of physiological saline, while in groups B and C were injected with 3µL (75µg) of bevacizumab and 3µL of bevacizumab-chitosan nanoparticles (containing 75µg of bevacizumab), respectively. Immunohistochemistry was used to assess retinal angiogenesis, real-time PCR assay was used to analyse the expression of VEGF mRNA, and light microscopy was used to evaluate the morphology of retinal capillaries.
  
  
  RESULTS
  Real-time PCR assay revealed that the VEGF mRNA expression in the retina before injection was similar to 1 week after injection in group A (P>0.05), while the VEGF mRNA expression before injection significantly differed from those 4 and 8 weeks after injection (P<0.05). Retinal expression of VEGF protein and VEGF mRNA was inhibited 1 week and 4 weeks after injection (P<0.05) in group B, and the expression of VEGF protein and VEGF mRNA was obviously inhibited until 8 weeks after injection (P<0.05) in group C. Using multiple comparisons among group A, group B, and group C, the VEGF expression before injection was higher than at 1, 4 and 8 weeks after injection (P<0.05). The amount of VEGF expression was higher 8 weeks after injection than 1 week or 4 weeks after injection, and also higher 1 week after injection compared with 4 weeks after injection (P<0.05). No toxic effect on SD rats was observed with bevacizumab-chitosan nanoparticles injection alone.
  
  
  CONCLUSIONS
  The results offer a new approach for inhibiting angiogenesis of diabetic retinopathy and indicate that the intravitreal injection of bevacizumab inhibits VEGF expression in retina, and bevacizumab-chitosan nanoparticles have a longer duration of action.
authors.affiliation: Department of Ophthalmology, Changzheng Hospital, the Second Affiliated Hospital of the Second Military Medical University, Shanghai 200003, China ; Department of Ophthalmology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, Jiangsu Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Ophthalmology, Changzheng Hospital, the Second Affiliated Hospital of the Second Military Medical University, Shanghai 200003, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Ophthalmology, Changzheng Hospital, the Second Affiliated Hospital of the Second Military Medical University, Shanghai 200003, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Ophthalmology, Changzheng Hospital, the Second Affiliated Hospital of the Second Military Medical University, Shanghai 200003, China.
authors.forename: Jin-Wei
authors.initials: JW
authors.lastname: Cheng
authors.affiliation: Department of Ophthalmology, Changzheng Hospital, the Second Affiliated Hospital of the Second Military Medical University, Shanghai 200003, China.
authors.forename: Feng-Qian
authors.initials: FQ
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Changzheng Hospital, the Second Affiliated Hospital of the Second Military Medical University, Shanghai 200003, China.
authors.forename: Rui-Li
authors.initials: RL
authors.lastname: Wei
authors.affiliation: Department of Ophthalmology, Changzheng Hospital, the Second Affiliated Hospital of the Second Military Medical University, Shanghai 200003, China.
authors.forename: Ji-Ping
authors.initials: JP
authors.lastname: Cai
keywords: bevacizumab; diabetic retinopathy; intravitreal injection; nanoparticles