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Abstract #9665 Published in IGR 5-3
In vitro effects of preserved and unpreserved antiglaucoma drugs on apoptotic marker expression by human trabecular cells
Hamard P; Blondin C; Debbasch C; Warnet JM; Baudouin C; Brignole FGraefe's Archive for Clinical and Experimental Ophthalmology 2003; 241: 1037-1043
BACKGROUND: The mechanisms of trabecular cell loss in glaucoma patients are poorly understood. In order to determine whether drug-induced apoptosis could be one of the mechanisms by which trabecular cells die in glaucoma, the authors evaluated the effect of benzalkonium-preserved (BAC+) or preservative-free (BAC-) antiglaucoma medications on apoptotic marker expression by cultured human trabecular meshwork (HTM) cells. METHODS: Normal and glaucomatous trabecular cell lines were treated for 15 minutes with antiglaucoma drugs (1/100 and 1/10 dilutions): timolol BAC+ or BAC-, betaxolol BAC+ or BAC-, latanoprost BAC+ or pure BAC. Apo2.7 expression, annexin V binding and DNA content were evaluated by flow cytometry and confocal microscopy. RESULTS: Results obtained in the two cell lines were similar for all tested drugs and criteria. In a 1/100 dilution, unpreserved beta-blockers had no apoptotic effect, preserved beta-blockers and latanoprost significantly increased Apo2.7 expression only, while BAC significantly increased all three apoptotic markers. When tested in a 1/10 dilution, all drugs except unpreserved timolol triggered a two- to 3.5-fold increase in apoptotic features, whereas up to 95% of the cells underwent apoptosis upon treatment with BAC (representing a nine-fold increase over the background level). CONCLUSIONS: At concentrations higher than those supposed to be found in the aqueous humor after instillation (1/100 dilution), unpreserved beta-blocker exhibited no proapoptotic activity on HTM cells in vitro. Benzalkonium-containing beta-blockers and prostaglandin analogue triggered mild expression of one out of three apoptotic markers, while the pro-apoptotic effect observed with BAC appeared to be largely hindered by active compounds in the preserved eye drops.
Dr. P. Hamard, Department of Ophthalmology, Quinze-Vingts Hospital, 28 rue de Charenton, 75012 Paris, France. pascale-hamard@quinze-vingts.fr
Classification:
2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
11.1 General management, indication (Part of: 11 Medical treatment)
