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1 General aspects (0)   1.1 Epidemiology (3)   1.2 Population genetics (1)   1.3 Pathogenesis (3)   1.4 Quality of life (4)   1.5 Glaucomas as cause of blindness (2)   1.6 Prevention and screening (4) 2 Anatomical structures in glaucoma (1)   2.1 Conjunctiva (1)   2.2 Cornea (8)   2.3 Sclera (1)   2.4 Anterior chamber angle (0)   2.5 Meshwork (0)     2.5.1 Trabecular meshwork (12)     2.5.2 Schlemms canal (1)     2.5.3 Scleral outlet channels (0)   2.6 Aqueous humor dynamics (3)     2.6.1 Production (0)     2.6.2 Outflow (1)       2.6.2.1 Trabecular meshwork (0)       2.6.2.2 Uveoscleral (0)     2.6.3 Compostion (2)   2.7 Episcleral veins and venous pressure (0)   2.8 Iris (0)   2.9 Ciliary body (3)   2.10 Lens (0)   2.11 Vitreous body (0)   2.12 Choroid, peripapillary choroid, peripapillary atrophy (0)   2.13 Retina and retinal nerve fibre layer (11)   2.14 Optic disc (5)   2.15 Optic nerve (2)   2.16 Chiasma and retrochiasmal central nervous system (2)   2.17 Stem cells (0)   2.20 Other (0) 3 Laboratory methods (8)   3.1 Microscopy (2)   3.2 Electron microscopy (0)   3.3 Immunohistochemistry (13)   3.4 Molecular genetics (0)     3.4.1 Linkage studies (10)     3.4.2 Gene studies (4)   3.5 Molecular biology incl. 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(10)

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Abstract #12354 Published in IGR 7-2

Effects of antiglaucoma drugs timolol and GLC756, a novel dopamine D₂ agonist and D₁ antagonist, on endotoxin-induced-uveitis in rats

Laengle UW; Markstein R; Schneider V; Greiner B; Roman D
Experimental Eye Research 2005; 80: 847-852

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Antiglaucoma drugs with anti-inflammatory properties may be of particular value for the long-term treatment of glaucoma since they may reduce the risk for treatment-related inflammatory processes in outer compartments of the eye. The purpose of this study was, to evaluate the effect of systemic and topical administration of GLC756, a novel mixed dopamine D₂ receptor agonist and D₁ receptor antagonist which lowered intraocular pressure in man, and timolol on endotoxin-induced-uveitis (EIU) in rats. For EIU, 8-week-old Lewis rats received an intravenous injection of 160 μg lipopolysaccharide (LPS) from Salmonella typhimurium. GLC756, timolol, or betamethasone, as positive control, were administered either topically (0.4, 0.5, and 0.1%, respectively, 16-times 20 microl eye drops during 48 hr) or systemically (1 mg kg^-1 subcutaneously for 5 days). Protein content, released TNF-α, the number of cells as well as cells expressing TNF-α were determined in aqueous humor 48 hr after LPS-injection and served as parameters for inflammation. LPS induced an increase of protein content, infiltrating cells and cells expressing TNF-α in the aqueous humor. Topical and systemic administration of GLC756 and betamethasone, almost completely suppressed the increase of protein content and betamethasone in addition also suppressed the number of cells in aqueous humor. In conclusion, the almost complete suppression of LPS-induced protein increase in aqueous humor by GLC756 suggests an additional anti-inflammatory potential of dopaminergic compounds in glaucoma treatment. Timolol did not show any effect on EIU in rats.

Dr. U.W. Laengle, Department of Toxicology/Pathology, Novartis Pharma AG, 4002-Basel, Switzerland. ulrich.laengle@pharma.novartis.com

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Classification:

11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)

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