Download PDF
Klin Monbl Augenheilkd 2003; 220(3): 156-160
DOI: 10.1055/s-2003-38168
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Transepithelial Short Circuit Currents in Human and Porcine Isolated Ciliary Bodies: Effect of Acetazolamide and Epinephrine

Transepitheliale Kurzschlussströme im isolierten Ziliarkörper des Menschen und des Schweines: Der Effekt von Acetazolamid und EpinephrinRenyi  Wu1 , Josef  Flammer1 , Ivan  Haefliger1
  • 1Laboratory of Ocular Pharmacology and Physiology, University Eye Clinic Basel (Director: Josef Flammer)
The authors thank Peter Meyer, MD and Reto Allemann, BS for their help in obtaining the human eyes
Further Information

Publication History

Eingegangen: 30. September 2002

Angenommen: 12. Dezember 2002

Publication Date:
28 March 2003 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Hintergrund: Die vorliegende Studie untersucht den Effekt von Acetazolamid und Epinephrin auf den transepithelialen Ionenfluss (ein Parameter, der die Kammerwasserproduktion widerspiegelt) im Ziliarkörper des Menschen und des Schweines. Material und Methoden: Isolierte Ziliarkörper wurden in einer Ussing-Kammer eingespannt, um die transepitheliale Potenzialdifferenz (PD) und die Kurzschlussströme (Isc) vor und nach Exposition mit 100 µM Acetazolamid oder 10 µM Epinephrin zu messen. Resultate: In menschlichen Ziliarkörpern (n = 27), war die Basislinien-PD (1184 ± 100 µV) auf der unpigmentierten Epithelium(NPE)-Seite negativ, der entsprechende Isc betrug 19,9 ± 1,5 µA/cm2. Acetazolamid (n = 7 - 8) erniedrigte Isc (NPE-Seite 8,4 ± 1,1 µA/cm2, pigmentierten Epithelium [PE]-Seite 7,4 ± 0,9 µA/cm2). Epinephrin (n = 6) erniedrigte den Isc nur auf der NPE-Seite um 9,9 ± 0,8 µA/cm2. Im Schweineziliarkörper war die Basislinien-PD in einigen Präparaten negativ (862 ± 84 µV, n = 18) und in anderen positiv (814 ± 81 µV, n = 10) auf der NPE-Seite mit Isc (15,6 ± 1,6 µA/cm2, respektive 16,3 ± 2,6 µA/cm2). In allen Präparaten erniedrigte Acetazolamid (n = 6 - 7) den Isc (NPE-Seite: 6,1 ± 0,6 µA/cm2; PE-Seite: 4,8 ± 0,3 µA/cm2), wogegen Epinephrin (n = 8) Isc nur auf der NPE-Seite (10,5 ± 0,6 µA/cm2) erhöhte. Schlussfolgerungen: In der vorliegenden Studie wurde erstmalig die Ussing-Kammer zur Messung von transepithelialen Ionenströmen am isolierten Ziliarkörper des Menschen und des Schweines verwendet. Eine zukünftige Anwendungsmöglichkeit der Methode liegt in der Untersuchung von Medikamenten, die die Kammerwasserproduktion beeinflussen.

Abstract

Background: To investigate in human and porcine isolated ciliary bodies the effect of acetazolamide and epinephrine on ciliary transepithelial ionic currents (a parameter linked to aqueous humor production). Material and methods: Isolated ciliary bodies were mounted in a Ussing-type chamber to measure transepithelial potential difference (PD) and short circuit current (Isc) before and after exposure to either 100 µM acetazolamide or 10 µM epinephrine. Results: In humans (N = 27), baseline PD was 1184 ± 100 µV (negative on the non-pigmented epithelial [NPE] side) and Isc 19.9 ± 1.5 µA/cm2. Acetazolamide (N = 7 - 8) decreased Isc (NPE side: 8.4 ± 1.1 µA/cm2; pigmented epithelial [PE] side: 7.4 ± 0.9 µA/cm2) while epinephrine (N = 6) increased Isc only on the NPE side (9.9 ± 0.8 µA/cm2). In pigs, baseline PD was in some preparations negative (862 ± 84 µV, N = 18) and in others positive (814 ± 81 µV, N = 10) on the NPE side with Isc 15.6 ± 1.6 µA/cm2 and 16.3 ± 2.6 µA/cm2, respectively. In all preparations, acetazolamide (N = 6 - 7) decreased Isc (NPE side: 6.1 ± 0.6 µA/cm2; PE side: 4.8 ± 0.3 µA/cm2) while epinephrine (N = 8) increased it only on the NPE side (10.5 ± 0.6 µA/cm2). Conclusions: To our knowledge, this is the first time that this methodology is applied to measure transepithelial ionic currents in isolated human and porcine ciliary bodies. This method could be used to test drugs modulating aqueous humor production.

Schlüsselwörter

Glaukom - Ziliarkörper - Kurzschlussstrom - Karbonanhydrase Inhibitor - Adrenorezeptoragonist

Key words

Glaucoma - ciliary process - short circuit current - carbonic anhydrase inhibitors - adrenoreceptor agonists

References

  • 1 Davson H. The physiology of the eye. 3rd ed. Edinburgh, London; Churchill Livingstone 1972
    Google Scholar
  • 2 Jacob T J, Civan M M. Role of ion channels in aqueous humor formation.  Am J Physiol Cell Physiol. 1996;  271 C703-C720
    PubMedGoogle Scholar
  • 3 Ussing H H, Zerahn K. Active transport of sodium as the source of electric current in the short-circuited isolated frog skin.  Acta Physiol Scand. 1951;  23 110-127
    CrossrefPubMedGoogle Scholar
  • 4 Kupfer C, Gaasterland D, Ross K. Studies of aqueous humor dynamics in man. V. Effects of acetazolamide and isoproterenol in young and old normal volunteers.  Invest Ophthalmol. 1976;  15 349-355
    PubMedGoogle Scholar
  • 5 Kacere R D, Dolan J W, Brubaker R F. Intravenous epinephrine stimulates aqueous formation in the human eye.  Invest Ophthalmol Vis Sci. 1992;  33 2861-2865
    PubMedGoogle Scholar
  • 6 Townsend D J, Brubaker R F. Immediate effects of epinephrine on an aqueous formation in the normal human eye as measured by fluorophotometry.  Invest Ophthalmol Vis Sci. 1980;  19 256-266
    PubMedGoogle Scholar
  • 7 Schenker H I, Yablonski M E, Podos S M, Linder L. Fluorophotometric study of epinephrine and timolol in human subjects.  Arch Ophthalmol. 1981;  99 1212-1216
    PubMedGoogle Scholar
  • 8 Wiederholt M, Zadunaisky J A. Effects of ouabain and furosemide on transepithelial electrical parameters of the isolated shark ciliary epithelium.  Invest Ophthalmol Vis Sci. 1987;  28 1353-1356
    PubMedGoogle Scholar
  • 9 Wiederholt M, Fluegel C, Fuetjen-drecoll E, Zadunaisky J A. Mechanically stripped pigmented and non-pigmented epithelium of the shark ciliary body: morphology and transepithelial electrical properties.  Exp Eye Res. 1989;  499 1031-1043
    PubMedGoogle Scholar
  • 10 Chu T C, Candia O A, Podos S M. Electrical parameters of the isolated monkey ciliary epithelium and effects of pharmacological agents.  Invest Ophthalmol Vis Sci. 1987;  28 1644-1648
    PubMedGoogle Scholar
  • 11 To C H, Do C W, Sumida A C, Candia O A. Model of ionic transport for bovine ciliary epithelium: effects of acetazolamide and HCO.  Am J Physiol Cell Physiol. 2001;  280 C1521-C1530
    PubMedGoogle Scholar
  • 12 McLaughlin C W, Peart D, Purves R D, Carre D A, Macknight A D, Civan M M. Effects of HCO3 - on cell composition of rabbit ciliary epithelium: a new model for aqueous humor secretion.  Invest Ophthalmol Vis Sci. 1998;  39 1631-1641
    PubMedGoogle Scholar
  • 13 Do C W, To C H. Chloride secretion by bovine ciliary epithelium: a model of aqueous humor formation.  Invest Ophthalmol Vis Sci. 2000;  41 1853-1860
    PubMedGoogle Scholar
  • 14 Bill A. Early effects of epinephrine on aqueous humor dynamics in vervet monkeys (Cercopithecus ethiops).  Exp Eye Res. 1969;  8 35-43
    PubMedGoogle Scholar
  • 15 Erickson-Lamy K A, Nathanson J A. Epinephrine increases facility of outflow and cyclic AMP content in the human eye in vivo.  Invest Ophthalmol Vis Sci. 1992;  33 2672-2678
    PubMedGoogle Scholar
  • 16 Chu T C, Candia O A. Effects of adrenergic agonists and cyclic AMP on the short-circuit current across the isolated rabbit iris-ciliary body.  Curr Eye Res. 1985;  4 523-529
    PubMedGoogle Scholar

Ivan O. Haefliger,MD 

Laboratory of Ocular Pharmacology and Physiology · University Eye Clinic Basel

Mittlere Straße 91

PO Box

4012 Basel · Switzerland