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Nonsulfhydryl-reactive phenoxyacetic acids increase aqueous humor outflow facility.

PURPOSE: The phenoxyacetic acid, ethacrynic acid (ECA), has potential use in glaucoma therapy because it acts to increase aqueous outflow in vivo and in vitro. In human trabecular meshwork (HTM) cell culture, ECA acts to change cell shape and attachment, effects that have been correlated with microtubule (MT) alterations and chemical sulfhydryl (SH) reactivity. To further explore these actions, we evaluated two non-SH reactive phenoxyacetic acids, inadcrinone and ticrynafen, and the MT-disrupting drug vinblastine. METHODS: Excised bovine and porcine eyes were perfused and outflow facility measured. Calf pulmonary artery endothelial and HTM cells were grown in culture and cytoskeletal effects evaluated after drug treatment. RESULTS: Indacrinone, ticrynafen, and vinblastine all caused an increase in outflow facility. In contrast with ECA, the outflow effects of indacrinone and ticrynafen were not blocked by excess cysteine. Although indacrinone and ticrynafen produced changes in cell shape in vitro, the beta-tubulin staining pattern of treated cells was not altered. Vinblastine caused cell shape change and the expected MT disruption. CONCLUSIONS: Phenoxyacetic acids can increase aqueous outflow facility and alter HTM cell shape and attachment in vitro by a non-SH, non-MT mechanism (which is probably shared also by ECA). These findings suggest the possibility of a broader class of glaucoma drugs that may be directed at the HTM. An understanding of the cellular target for these drugs has implications both for potential glaucoma therapy and for the cytoskeletal mechanisms involved in normal outflow function.

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Kynurenine and neopterin in the aqueous humor of the anterior chamber of the eye and in serum of cataract patients.

Serum kynurenine, neopterin, selenium concentrations; neopterin concentrations in aqueous humour from anterior chamber of eye and selenium content in lenses were determined in 40 catarat patients with and in 51--without pseudoexfoliation (PES). Significantly increased kynurenine and neopterin levels in serum and neopterin concentration in aqueous humour were observed in mature cataract patients with PES compared to whose without. These patients also presented with the lowest content of selenium in serum and lens, compared with cataract patients without PES. Increased concentrations of neopterin in serum and aqueous humour of anterior chamber of eyes suggest an increased degree of oxidative stress in patients with PES. Thus, the results support the role of oxidative stress in the development of PES in cataract patients. The decreased content of selenium may elicit immune system activation via an increased oxidative stress as it is indicated by the increased formation of kynurenine and neopterin.

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Quantitation of specific antibodies in the aqueous humor.

Six normal rabbits were injected intravitreally with bovine gamma-globulin (BGG). Quantitation of immunoglobulins A, M and G, in the aqueous and in the serum, was performed by the single radial immunodiffusion following the method described by MANCINI et. al. Concentration of anti-BGG antibodies was determined by the reversed Mancini method. The antibody quotient was calculated; it reached to 8 and 5.96 in the aqueous of the injected eyes 10 days after intravitreal injection, 22.69 and 24 days, 22.52 after 28 days and 14.93 after 31 days.

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