title: A novel approach to attenuate proliferative vitreoretinopathy using ultrasound-targeted microbubble destruction and recombinant adeno-associated virus-mediated RNA interference targeting transforming growth factor-β2 and platelet-derived growth factor-B.
abstract: BACKGROUND
  To date, with the exception of surgery, there are no satisfactory treatments available for proliferative vitreoretinopathy (PVR). Ultrasound-targeted microbubble destruction (UTMD) represents a new approach for the gene therapy of eye diseases. The present study aimed to investigate the feasibility of the attenuation of PVR by a combinatorial use of UTMD and recombinant adeno-associated virus (rAAV)-mediated RNA interference (RNAi) targeting transforming growth factor (TGF)-β2 and platelet-derived growth factor (PDGF)-B.
  
  
  METHODS
  One hundred and eighty rats of the PVR model were averagely divided into six groups (G). The left eyes, respectively, received an intravitreal injection as follows: normal saline (G1), rAAV2-control small interfering RNA (siRNA) (G2), rAAV2-TGF-β2-siRNA (G3), rAAV2-PDGF-B-siRNA (G4), rAAV2-TGF-β2-siRNA and rAAV2-PDGF-B-siRNA (G5, G6) on day 3 after PVR induction. In G6, a condition of UTMD was used additionally. On days 14 and 28, pathological changes of eye fundus were assessed by ophthalmoscopic and histopathologic examination, and the protein and mRNA levels of TGF-β2 and PDGF-B expression were tested using enzyme-linked immunosorbent assay and a reverse transcriptase-polymerase chain reaction, respectively.
  
  
  RESULTS
  The average grade scales of proliferation and the protein and mRNA expression levels of TGF-β2 and PDGF-B in G6 were all lower than that in G5 on day 28 (p<0.05, unpaired t-test). They were all lower in G5 and G6 than in G1, G2, G3 and G4 on day 28 (p<0.05, one-way analysis of variance), although the protein and mRNA expression levels of PDGF-B in G6 did not differ from that in G1, G2, G3, G4 and G5 on day 14.
  
  
  CONCLUSIONS
  The combinatorial use of UTMD and rAAV2-mediated RNAi targeting TGF-β2 and PDGF-B can serve as a novel approach to attenuate PVR.
authors.affiliation: Department of Ultrasound, The Fourth Affiliated Hospital of Nantong University, Yancheng, Jiangsu Province, People's Republic of China.
authors.forename: Xiaozhi
authors.initials: X
authors.lastname: Zheng
authors.forename: Lianfang
authors.initials: L
authors.lastname: Du
authors.forename: Huiping
authors.initials: H
authors.lastname: Wang
authors.forename: Qing
authors.initials: Q
authors.lastname: Gu
mesh_terms: D000818:Animals; D000229:Dependovirus; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008297:Male; D045423:Microbubbles / Q000627:therapeutic use; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000378:metabolism; D018084:Ultrasonography, Interventional; D018630:Vitreoretinopathy, Proliferative / Q000235:genetics / Q000628:therapy
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D034741:RNA, Small Interfering; D053781:Transforming Growth Factor beta2