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Therapy with ribozyme to the proliferating cell nuclear antigen-ribozyme and 5-fluorouracil of experimental choroidal neovascularization in rats.

AbstractPURPOSE:
The aim of this study was to evaluate the efficacy of hammerhead ribozyme to the proliferating cell nuclear antigen (PCNA-Rz) and 5-fluorouracil (5-FU) in experimental choroidal neovascularization (CNV) model in rats.
METHODS:
Laser was used to induce CNV in each eye of 44 rats. For angiography studies, injections of either a mixture of PCNA-Rz 10 microg/microL and 5-FU 1.5 microg/microL, versus the same dose of either drug alone versus a control injection of Hanks' Balanced Salt Solution (HBSS) were performed. We also studied this regimen to evaluate scar size and volume.
RESULTS:
There was significantly less angiographic leakage for the treated eyes compared to the controls by 3.53 grading points (P = 0.0005); CNV leakage was reduced in the combination group compared to 5-FU alone by 1.75 grading units (P = 0.04) and compared to PCNARz by 2.22 grading units (P = 0.07). The scar size and volume were smaller (diameter 354.6 +/- 174.2 microm vs 477.3 +/- 157.0 microm), (thickness 52.7 +/- 43.0 microm versus 79.6 +/- 46.2 microm) with a reduction in scar volume of 44.8%.
CONCLUSIONS:
Subretinal injection of PCNA-Rz and 5-FU mixture is more effective as treatment of laser-induced CNV, than either drug alone. The majority of the antiangiogenic effect is a result of 5-FU activity with a contribution by the PCNA ribozyme.
AuthorsOzcan R Kayikcioglu, Iryna Falkenstein, Linguen Cheng, Igor Kozak, Laurie La Bree, Stanley P Azen, Flossie Wong-Staal, Nicholas F Paoni, William R Freeman
JournalJournal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics (J Ocul Pharmacol Ther) Vol. 22 Issue 1 Pg. 1-9 (Feb 2006) ISSN: 1080-7683 [Print] United States
PMID16503769 (Publication Type: Journal Article)
Chemical References
  • Antimetabolites, Antineoplastic
  • Proliferating Cell Nuclear Antigen
  • RNA, Catalytic
  • hammerhead ribozyme
  • Fluorouracil
Topics
  • Animals
  • Antimetabolites, Antineoplastic (therapeutic use)
  • Choroidal Neovascularization (therapy)
  • Combined Modality Therapy
  • Disease Models, Animal
  • Fluorescein Angiography
  • Fluorouracil (therapeutic use)
  • Male
  • Proliferating Cell Nuclear Antigen (genetics)
  • RNA, Catalytic (therapeutic use)
  • Rats
  • Rats, Long-Evans

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