IOVS Am. J. Pathology
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(Investigative Ophthalmology and Visual Science. 2008;49:250-254.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-1337
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Drug Modification of Angiogenesis in a Rat Cornea Model

Shulamit Schwartz,1,2 Jacob George,2,3 Jeremy Ben-Shoshan,2,3 Galia Luboshits,2,3 Isaac Avni,1,2 Hani Levkovitch-Verbin,2,4 Hana Ziv,2,4 Mordechai Rosner,2,4 and Adiel Barak2,5

1From the Department of Ophthalmology, Assaf Harofeh Medical Center, Zrifin, Israel; the 3Departments of Cardiology and 5Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; the 4Goldschleger Eye Research Institute, Sheba Medical Center, Tel Hashomer, Israel, and the 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

PURPOSE. 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, β-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.






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Copyright © 2008 by the Association for Research in Vision and Ophthalmology