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Abstract #5463 Published in IGR 1-2
Combined effects of H-7 and cytochalasin B on outflow facility in monkeys
Tian B; Gabelt BT; Geiger B; Kaufman PLExperimental Eye Research 1999; 66: 649-655
The serine-threonine protein kinase inhibitor H-7 and the fungal metabolite cytochalasin B (CB) disrupt the actin microfilament network by different mechanisms, and increase outflow facility similarly in live monkeys. Their combined effect has therefore determined on total outflow facility in cynomolgus monkeys by 2-level constant pressure perfusion. (1) After unilateral anterior chamber (AC) bolus injection of H-7 (10 ?m, 100 ?m (subthreshold for increasing facility when given alone) or 500 ?m (just-threshold) followed by bilateral AC bolus injection of CB (2 ?g (strong but submaximal for increasing facility when given alone)), no significant difference between eyes was observed. (2) After bilateral AC exchange with a subthreshold dose of H-7 (10 ?m) followed by unilateral AC bolus injection of a subthreshold dose of CB (0.02, 0.05, 0.1 or 0.5 ?g), 10 ?m H-7 plus 0.1 or 0.5 ?g CB increased facility by approximately 40 or 80% compared to 10 ?m H-7 alone. (3) After bilateral AC exchange with a maximal dose of H-7 (300 ?m), followed by unilateral AC bolus injection of a subthreshold dose of CB (0.1 or 0.5 ?g), 300 ?m H-7 plus 0.5 ?g CB increased outflow facility by 47% compared to 300 ?m H-7 alone. (4) After unilateral AC exchange with a maximal dose of H-7 (300 ?m) followed by bilateral AC bolus injection of a near-maximal dose of CB (2 ?g), 300 ?m H-7 plus 2 ?g CB increased the facility by 67% compared to 2 ?g CB alone. The significant effect of combined subthreshold doses of H-7 and CB on outflow facility, the potentiation of the facility-increasing effect of a maximal H-7 dose by both subthreshold and near-maximal CB doses, and the known cytoskeletal effects of both compounds, may suggest that both increase facility by disrupting actin filaments in the trabecular meshwork.
B. Tian, Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI; USA
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)