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Subconjunctival Administration of Bucillamine Suppresses Choroidal Neovascularization in Rat

¹ From the Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan; the ² Department of Regenerative Medicine, Research Institute, International Medical Center of Japan, Tokyo, Japan; and the ³ Ophthalmic Research Division, Santen Pharmaceutical Co., Ltd., Nara Research and Development Center, Ikoma-shi, Japan.

PURPOSE. Bucillamine is an antirheumatic drug with antiangiogenic properties that is currently used in clinical practice. Because bucillamine inhibits the production of VEGF, it is possible that this drug may inhibit choroidal neovascularization (CNV). Thus, the effect of bucillamine on the eyes of rats with experimental CNV was investigated in vivo by subconjunctival injection or oral intake.

METHODS. CNV was induced in rat eyes by diode laser photocoagulation. The intensity of fluorescein leakage from the photocoagulated lesions was studied 7 and 14 days after photocoagulation. The areas of CNV lesions were measured histologically and studied immunohistochemically at days 4, 7, and 14. In addition, the concentration of the drug in ocular tissue and blood was measured by high-performance liquid chromatography–tandem mass spectrometry after the drug was delivered orally or subconjunctivally.

RESULTS. After subconjunctival injection, fluorescein leakage from the CNV lesions decreased significantly compared with the control eyes throughout the study period. Histologic and immunohistochemical analyses 4, 7, and 14 days after photocoagulation demonstrated that the average size of the CNV lesions was reduced in the bucillamine-treated eyes compared with the control eyes. Subconjunctival injection maximized the ocular drug concentration while minimizing the blood concentration of the drug compared with oral intake.

CONCLUSIONS. Subconjunctival injection of bucillamine significantly reduced the leakage and size of experimental CNV. These results suggest that bucillamine may be beneficial in treating CNV and that further studies can be considered to evaluate this possibility.

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