Drug modification of angiogenesis in a rat cornea model.
OBJECTIVE
To evaluate the influence of some widely used antiglaucoma agents on angiogenesis in a novel rat cornea model.


METHODS
Angiogenesis was induced in 32 rats by slow-release polymer pellets containing basic fibroblast growth factor (bFGF) placed in a corneal micropocket. Angiogenesis was later measured and compared in groups of rats given one of four antiglaucoma drug therapies and one control group. The drugs were commercially available preparations of prostaglandins, beta-blockers, alpha-2 agonists, and carbonic anhydrase inhibitors given for 7 days in a manner similar to that used in humans. Growth was measured by calculating the maximum linear vessel growth divided by pellet-limbus distance.


RESULTS
Biomicroscopic observation disclosed that all tested animals showed an induction of neovascular reactions in their corneal stroma. The growth index results for the control, latanoprost, dorzolamide, brimonidine, and timolol malate groups were 1.65 +/- 0.16, 1.98 +/- 0.18, 1.85 +/- 0.19, 2.03 +/- 0.38, and 1.65 +/- 0.14, respectively, confirming the hypothesis that topically delivered antiglaucoma drugs modify the normal angiogenic response. Of them, the prostaglandins showed the most prominent angiogenic stimulatory effect (P = 0.03).


CONCLUSIONS
This modified micropocket assay of corneal angiogenesis in rats demonstrated the stimulatory effect of several widely used topically delivered antiglaucoma medications on the angiogenic process. The results indicate that the selection of drugs for treating different ophthalmic diseases should take into account their influence on angiogenic processes.
Schwartz
Shulamit
S
Department of Ophthalmology, Assaf Harofeh Medical Center, 6 Weizman Street, Zrifin, Israel.
George
Jacob
J
Ben-Shoshan
Jeremy
J
Luboshits
Galia
G
Avni
Isaac
I
Levkovitch-Verbin
Hani
H
Ziv
Hana
H
Rosner
Mordechai
M
Barak
Adiel
A
D000818:Animals; D000959:Antihypertensive Agents / Q000633:toxicity*; D000068438:Brimonidine Tartrate; D016510:Corneal Neovascularization / Q000503:physiopathology*; D003319:Corneal Stroma / Q000098:blood supply* / Q000187:drug effects; D004195:Disease Models, Animal; D004343:Drug Implants; D016222:Fibroblast Growth Factor 2 / Q000633:toxicity; D000077338:Latanoprost; D011461:Prostaglandins F, Synthetic / Q000633:toxicity; D011810:Quinoxalines / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000633:toxicity; D013876:Thiophenes / Q000633:toxicity; D013999:Timolol / Q000633:toxicity
D000959:Antihypertensive Agents; D004343:Drug Implants; D011461:Prostaglandins F, Synthetic; D011810:Quinoxalines; D013449:Sulfonamides; D013876:Thiophenes; D016222:Fibroblast Growth Factor 2; D000068438:Brimonidine Tartrate; D000077338:Latanoprost; D013999:Timolol; C062765:dorzolamide