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Ethacrynic Acid Increases Facility of Outflow in the Human Eye In Vitro

Ethacrynic Acid Increases Facility of Outflow in the Human Eye In Vitro Abstract • Anterior segments of human donor eyes were perfused with culture medium at a perfusion pressure of 15 mm Hg in a 5% carbon dioxide environment at 37°C. After determination of a baseline facility of outflow, the perfusion chamber contents were exchanged with either drug vehicle or ethacrynic acid, at concentrations ranging from 0.01 to 0.25 mmol/L, after which postdrug facility was measured in the continuous presence of drug vehicle or ethacrynic acid. Ethacrynic acid increased facility of outflow from 28% to 105% at ethacrynic acid concentrations of 0.01 to 0.25 mmol/L, respectively. No morphologic correlate of the facility increase was observed with 0.01mmol/L ethacrynic acid, nor were there any signs of cellular toxic effects. At 0.1 mmol/L, separations between trabecular meshwork cells and breaks between inner-wall cells were observed. At 0.25 mmol/L, focal areas of cell swelling and necrosis were noted. This study demonstrated that ethacrynic acid increases outflow facility in the aged human eye at concentrations that produce no apparent toxic effects. Therefore, ethacrynic acid may potentially prove useful in the treatment of glaucoma. References 1. Epstein DL, Freddo TF, Bassett-Chu, Chung M, Karageuzian L. Influence of ethacrynic acid on outflow facility in the monkey and calf eye . Invest Ophthalmol Vis Sci . 1987;28:2067-2075. 2. Erickson-Lamy K, Rohen JW, Grant WM. Outflow facility studies in the perfused bovine aqueous outflow pathways . Curr Eye Res . 1988;7:799-807.Crossref 3. Erickson-Lamy K, Rohen JW, Grant WM. Outflow facility studies in the perfused human ocular anterior segment . Exp Eye Res . 1991;52:723-731.Crossref 4. Erickson-Lamy KA, Ostovar B, Hunnicutt EJ, Nathanson JA. Epinephrine increases facility of outflow and trabecular meshwork cAMP content in the human eye in vitro . Invest Ophthalmol Vis Sci . 1990;31( (suppl) ):184. Abstract. 5. Rohen JW. The histologic structure of the chamber angle in primates . Am J Ophthalmol . 1961;52:529-539. 6. Rohen JW. Morphology of the uveal tract . Int Ophthalmol Clin . 1965;5:581-667.Crossref 7. Erickson-Lamy K, Schroeder A, Epstein DL. Ethacrynic acid induces a reversible shape change and cytoskeletal changes in cultured cells . Invest Ophthalmol Vis Sci . 1987;28( (suppl) ):283. Abstract. 8. Schroeder A, Erickson-Lamy K, Epstein DL. Ethacrynic acid induced changes in cytoskeletal tubulin . Invest Ophthalmol Vis Sci . 1989;30( (suppl) ):356. Abstract. 9. Svedbergh B, Lütjen-Drecoll E, Oberr M, Kaufman PL. Cytochalasin B-induced structural changes in the anterior ocular segment of the Cynomolgus monkey . Invest Ophthalmol Vis Sci . 1987;17:718-734. 10. Kaufman PL, Bárány EH. Cytochalasin B reversibly increases outflow facility in the eye of the cynomolgus monkey . Invest Ophthalmol Vis Sci . 1977;16:47-53. 11. Kaufman PL, Bill A, Bárány EH. Effect of cytochalasin B on conventional drainage of aqueous humor in the cynomolgus monkey: the ocular and cerebrospinal fluids . Exp Eye Res . 1977;25( (suppl) ):411-414.Crossref 12. Kaufman PL, Erickson K. Cytochalasin B and D dose-outflow facility response relationships in the cynomolgus monkey . Invest Ophthalmol Vis Sci . 1982;23:646-650. 13. Bill A, Lütjen-Drecoll E, Svedbergh B. Effects of intracameral Na2 EDTA and EGAT on aqueous outflow routes in the monkey eye . Invest Ophthalmol Vis Sci . 1980;19:492-504. 14. Hamanaka T, Bill A. Morphological and functional effects of Na2EDTA on the outflow routes for aqueous humor in monkeys . Exp Eye Res . 1987;44:171-190.Crossref 15. Ryder MI, Weinreb RN, Alvarado J, Polansky J. The cytoskeleton of the cultured human trabecular cell . Invest Ophthalmol Vis Sci . 1988;29:251-260. 16. Perkins TW, Alvarado JA, Polansky JR, Stilwell L, Maglio M, Luster R. Trabecular meshwork cells grown on filters . Invest Ophthalmol Vis Sci . 1988;29:1836-1846. 17. Weinreb RN, Ryder MI, Polansky JR. The cytoskeleton of the cynomolgus monkey trabecular cell . Invest Ophthalmol Vis Sci . 1986;27:1312-1317. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Ophthalmology American Medical Association

Ethacrynic Acid Increases Facility of Outflow in the Human Eye In Vitro

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Publisher
American Medical Association
Copyright
Copyright © 1992 American Medical Association. All Rights Reserved.
ISSN
0003-9950
eISSN
1538-3687
DOI
10.1001/archopht.1992.01080130108036
Publisher site
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Abstract

Abstract • Anterior segments of human donor eyes were perfused with culture medium at a perfusion pressure of 15 mm Hg in a 5% carbon dioxide environment at 37°C. After determination of a baseline facility of outflow, the perfusion chamber contents were exchanged with either drug vehicle or ethacrynic acid, at concentrations ranging from 0.01 to 0.25 mmol/L, after which postdrug facility was measured in the continuous presence of drug vehicle or ethacrynic acid. Ethacrynic acid increased facility of outflow from 28% to 105% at ethacrynic acid concentrations of 0.01 to 0.25 mmol/L, respectively. No morphologic correlate of the facility increase was observed with 0.01mmol/L ethacrynic acid, nor were there any signs of cellular toxic effects. At 0.1 mmol/L, separations between trabecular meshwork cells and breaks between inner-wall cells were observed. At 0.25 mmol/L, focal areas of cell swelling and necrosis were noted. This study demonstrated that ethacrynic acid increases outflow facility in the aged human eye at concentrations that produce no apparent toxic effects. Therefore, ethacrynic acid may potentially prove useful in the treatment of glaucoma. References 1. Epstein DL, Freddo TF, Bassett-Chu, Chung M, Karageuzian L. Influence of ethacrynic acid on outflow facility in the monkey and calf eye . Invest Ophthalmol Vis Sci . 1987;28:2067-2075. 2. Erickson-Lamy K, Rohen JW, Grant WM. Outflow facility studies in the perfused bovine aqueous outflow pathways . Curr Eye Res . 1988;7:799-807.Crossref 3. Erickson-Lamy K, Rohen JW, Grant WM. Outflow facility studies in the perfused human ocular anterior segment . Exp Eye Res . 1991;52:723-731.Crossref 4. Erickson-Lamy KA, Ostovar B, Hunnicutt EJ, Nathanson JA. Epinephrine increases facility of outflow and trabecular meshwork cAMP content in the human eye in vitro . Invest Ophthalmol Vis Sci . 1990;31( (suppl) ):184. Abstract. 5. Rohen JW. The histologic structure of the chamber angle in primates . Am J Ophthalmol . 1961;52:529-539. 6. Rohen JW. Morphology of the uveal tract . Int Ophthalmol Clin . 1965;5:581-667.Crossref 7. Erickson-Lamy K, Schroeder A, Epstein DL. Ethacrynic acid induces a reversible shape change and cytoskeletal changes in cultured cells . Invest Ophthalmol Vis Sci . 1987;28( (suppl) ):283. Abstract. 8. Schroeder A, Erickson-Lamy K, Epstein DL. Ethacrynic acid induced changes in cytoskeletal tubulin . Invest Ophthalmol Vis Sci . 1989;30( (suppl) ):356. Abstract. 9. Svedbergh B, Lütjen-Drecoll E, Oberr M, Kaufman PL. Cytochalasin B-induced structural changes in the anterior ocular segment of the Cynomolgus monkey . Invest Ophthalmol Vis Sci . 1987;17:718-734. 10. Kaufman PL, Bárány EH. Cytochalasin B reversibly increases outflow facility in the eye of the cynomolgus monkey . Invest Ophthalmol Vis Sci . 1977;16:47-53. 11. Kaufman PL, Bill A, Bárány EH. Effect of cytochalasin B on conventional drainage of aqueous humor in the cynomolgus monkey: the ocular and cerebrospinal fluids . Exp Eye Res . 1977;25( (suppl) ):411-414.Crossref 12. Kaufman PL, Erickson K. Cytochalasin B and D dose-outflow facility response relationships in the cynomolgus monkey . Invest Ophthalmol Vis Sci . 1982;23:646-650. 13. Bill A, Lütjen-Drecoll E, Svedbergh B. Effects of intracameral Na2 EDTA and EGAT on aqueous outflow routes in the monkey eye . Invest Ophthalmol Vis Sci . 1980;19:492-504. 14. Hamanaka T, Bill A. Morphological and functional effects of Na2EDTA on the outflow routes for aqueous humor in monkeys . Exp Eye Res . 1987;44:171-190.Crossref 15. Ryder MI, Weinreb RN, Alvarado J, Polansky J. The cytoskeleton of the cultured human trabecular cell . Invest Ophthalmol Vis Sci . 1988;29:251-260. 16. Perkins TW, Alvarado JA, Polansky JR, Stilwell L, Maglio M, Luster R. Trabecular meshwork cells grown on filters . Invest Ophthalmol Vis Sci . 1988;29:1836-1846. 17. Weinreb RN, Ryder MI, Polansky JR. The cytoskeleton of the cynomolgus monkey trabecular cell . Invest Ophthalmol Vis Sci . 1986;27:1312-1317.

Journal

Archives of Ophthalmology – American Medical Association

Published: Jan 1, 1992

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