Therapy with ribozyme to the proliferating cell nuclear antigen-ribozyme and 5-fluorouracil of experimental choroidal neovascularization in rats.
OBJECTIVE
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.
Kayikcioglu
Ozcan R
OR
Department of Ophthalmology, UCSD/Shiley Eye Center, La Jolla, CA 92037, USA.
Falkenstein
Iryna
I
Cheng
Linguen
L
Kozak
Igor
I
La Bree
Laurie
L
Azen
Stanley P
SP
Wong-Staal
Flossie
F
Paoni
Nicholas F
NF
Freeman
William R
WR
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D020256:Choroidal Neovascularization / Q000628:therapy*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005451:Fluorescein Angiography; D005472:Fluorouracil / Q000627:therapeutic use*; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics*; D016337:RNA, Catalytic / Q000627:therapeutic use*; D051381:Rats; D020318:Rats, Long-Evans
D000964:Antimetabolites, Antineoplastic; D018809:Proliferating Cell Nuclear Antigen; D016337:RNA, Catalytic; C427204:hammerhead ribozyme; D005472:Fluorouracil