Our hypotheses are that: 1) cellular sulfhydryl (-SH) groups in the trabecular meshwork (TM) are intimately involved in the process of aqueous humor outflow and may be subject to pharmacological manipulation for the potential treatment of open angle glaucoma. 2) a potential mechanism for the modulation of the outflow of aqueous humor might involve the oxidation and reduction of cellular -SH groups in the TM unde the influence of intracellular glutathione and extracellular hydrogen peroxide and ascorbic acid. 3) there are multiple potential sites in the TM for these -SH effects to occur, which likely involve changes in cell size and shape and cell to cell attachment in the deeper meshwork tissue and possibly the collector channels. 4) the good correlation of in vivo monkey and in vitro enucleated calf eye data substantiates the usefulness of the later as an alternative means for study of compounds which affect the aqueous humor outflow process. We will explore the usefulness of ethacrynic acid (ECA) as a potential antiglaucoma therapy and use it as a pharmacological """"""""probe"""""""" to help us better understand TM function. Repetitive topical, iontophoretic and intracameral applications of ECA will be made to living rabbits and monkeys and correlations sought to tissue culture and in vitro biochemical studies. We wish to better define -SH effects on cellular microfilments and on cell to cell and cell to substratum attachments. Possible secondary effects of calcium homeostasis will be explored. The effect on outflow function of SH containing compounds such as cysteamine will be studied as well as the interactions of SH reactive compounds and the effect of oxidative influences. In these studies aqueous human outflow faciliy will be measured in enucleated calf, monkey, and human eye as well as living monkeys and morphological correlates sought by electron microscopy.
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