Klin Monbl Augenheilkd 2018; 235(02): 140-145
DOI: 10.1055/s-0043-124084
Übersicht
Georg Thieme Verlag KG Stuttgart · New York

Stellenwert von Endothelin-1 beim Glaukom – ein kurzer Überblick

Significance of Endothelin-1 in Glaucoma – a Short Overview
Konstantin Gugleta
Augenklinik, Universitätsspital Basel, Schweiz
› Author Affiliations
Further Information

Publication History

eingereicht 13 October 2017

akzeptiert 28 November 2017

Publication Date:
15 February 2018 (online)

Zusammenfassung

Dieser Review-Artikel fokussiert sich auf verschiedene Aspekte der Endothelinrollen bei einem Glaukom; auf die Beteiligung von Endothelin bei anderen, vor allem vaskulären okulären Erkrankungen wird in diesem Artikel nicht im Detail eingegangen. Endothelin ist ein ubiquitäres Molekül, das in praktisch allen okulären Geweben vorhanden ist. Seine primäre physiologische Rolle ist die Steuerung des Gefäßdurchmessers und somit die Regulierung der Gewebedurchblutung. Sowohl die Sekretion als auch die Effekte des Endothelins finden lokal statt; ein Teil des Endothelins gelangt zwar in die systemische Zirkulation, jedoch ist dieser Teil variabel. Somit ist die Messung des Plasmaendothelinspiegels im venösen Blut nicht ideal für die Einschätzung der Endothelinfunktion, sowohl bei einzelnen Patienten als auch in Studienkohorten. Im Kontext der Glaukompathogenese lassen sich die wichtigsten Funktionen des Endothelins im Auge in Regulation des Augeninnendruckes, Regulation der Durchblutung und Aktivierung der Gliazellen/Astrozyten im hinteren Segment, in der Netzhaut und im Sehnerv einteilen. Bei so einem breiten Spektrum der Funktionen, die direkt bei der Pathogenese des Glaukoms involviert sind, liegt es auf der Hand, dass künftige therapeutische Ansätze beim Glaukom eine pharmakologische Modulation des Endothelins beinhalten sollten. Zu diesem Zweck ist derzeit die entsprechende Anwendung der zur Verfügung stehenden Endothelinantagonisten durch ihr ungünstiges Nebenwirkungsprofil beeinträchtigt.

Abstract

This review article is focused on the various facets of possible endothelinʼs role in glaucoma; involvement of endothelin in other ocular, in particular vascular, diseases is not specifically discussed. Endothelin is an ubiquitous molecule that occurs in practically all ocular tissues. Its primary physiological function is regulation of the blood vessel diameter and hence regulation of the blood supply in tissues. It is secreted locally, and exerts its effect also predominantly locally. This limits the value of venous blood sampling for estimation of the endothelin function in a particular patient, or in study cohorts as well. Endothelin is involved in the regulation of intraocular pressure, in the regulation of blood flow and in activation of retinal and optic nerve head astrocytes. All these functions are of high importance when it comes to pathogenesis of glaucoma. Possible future directions for glaucoma treatment should encompass pharmacological antagonism to endothelin, an avenue which is at present hindered by potentially serious side-effects of available endothelin-antagonists.

 
  • Literatur

  • 1 von Graefe A. Ueber die Iridektomie beim Glaukom und ueber den glaukomatösen Prozess. Arch Ophthalmol 1857; 3: 470
  • 2 Yanagisawa M, Kurihara H, Kimura S. et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988; 332: 411-415 doi:10.1038/332411a0
  • 3 Inoue A, Yanagisawa M, Kimura S. et al. The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci U S A 1989; 86: 2863-2867
  • 4 Haselhorst R, Kappos L, Bilecen D. et al. Dynamic susceptibility contrast MR imaging of plaque development in multiple sclerosis: application of an extended blood-brain barrier leakage correction. J Magn Reson Imaging 2000; 11: 495-505
  • 5 Shoshani YZ, Harris A, Shoja MM. et al. Endothelin and its suspected role in the pathogenesis and possible treatment of glaucoma. Curr Eye Res 2012; 37: 1-11 doi:10.3109/02713683.2011.622849
  • 6 Hu RM, Levin ER, Pedram A. et al. Atrial natriuretic peptide inhibits the production and secretion of endothelin from cultured endothelial cells. Mediation through the C receptor. J Biol Chem 1992; 267: 17384-17389
  • 7 Horio T, Kohno M, Takeda T. Effects of arginine vasopressin, angiotensin II and endothelin-1 on the release of brain natriuretic peptide in vivo and in vitro. Clin Exp Pharmacol Physiol 1992; 19: 575-582
  • 8 Ohta K, Hirata Y, Imai T. et al. Cytokine-induced release of endothelin-1 from porcine renal epithelial cell line. Biochem Biophys Res Commun 1990; 169: 578-584
  • 9 Just A, Olson AJ, Falck JR. et al. NO and NO-independent mechanisms mediate ETB receptor buffering of ET-1-induced renal vasoconstriction in the rat. Am J Physiol Regul Integr Comp Physiol 2005; 288: R1168-R1177 doi:10.1152/ajpregu.00550.2004
  • 10 Magazine HI, Srivastava KD. Thrombin-induced vascular reactivity is modulated by ETB receptor-coupled nitric oxide release in rat aorta. Am J Physiol 1996; 271: C923-C928
  • 11 Corder R, Carrier M, Khan N. et al. Cytokine regulation of endothelin-1 release from bovine aortic endothelial cells. J Cardiovasc Pharmacol 1995; 26 (Suppl. 03) S56-S58
  • 12 Cheng TH, Shih NL, Chen SY. et al. Reactive oxygen species mediate cyclic strain-induced endothelin-1 gene expression via Ras/Raf/extracellular signal-regulated kinase pathway in endothelial cells. J Mol Cell Cardiol 2001; 33: 1805-1814 doi:10.1006/jmcc.2001.1444
  • 13 Morawietz H, Talanow R, Szibor M. et al. Regulation of the endothelin system by shear stress in human endothelial cells. J Physiol 2000; 525: 761-770
  • 14 Okafor MC, Mukhopadhyay P, Delamere NA. Studies on endothelin release and Na,K transport in porcine lens. Invest Ophthalmol Vis Sci 2002; 43: 790-796
  • 15 Zhang X, Clark AF, Yorio T. Interactions of endothelin-1 with dexamethasone in primary cultured human trabecular meshwork cells. Invest Ophthalmol Vis Sci 2003; 44: 5301-5308
  • 16 Wollensak G, Löffler B, Beyermann B. et al. An immunohistochemical study of endothelin-1 converting enzyme in the human eye. Curr Eye Res 2002; 24: 6-11
  • 17 Fernandez-Durango R, Rollin R, Mediero A. et al. Localization of endothelin-1 mRNA expression and immunoreactivity in the anterior segment of human eye: expression of ETA and ETB receptors. Mol Vis 2003; 9: 103-109
  • 18 Kuhlmann A, Amann K, Schlötzer-Schrehardt U. et al. Endothelin-1 and ETA/ETB receptor protein and mRNA: expression in normal and vascularized human corneas. Cornea 2005; 24: 837-844
  • 19 Narayan S, Prasanna G, Krishnamoorthy RR. et al. Endothelin-1 synthesis and secretion in human retinal pigment epithelial cells (ARPE-19): differential regulation by cholinergics and TNF-alpha. Invest Ophthalmol Vis Sci 2003; 44: 4885-4894
  • 20 Stitt AW, Chakravarthy U, Gardiner TA. et al. Endothelin-like immunoreactivity and receptor binding in the choroid and retina. Curr Eye Res 1996; 15: 111-117
  • 21 Ripodas A, de Juan JA, Roldan-Pallares M. et al. Localisation of endothelin-1 mRNA expression and immunoreactivity in the retina and optic nerve from human and porcine eye. Evidence for endothelin-1 expression in astrocytes. Brain Res 2001; 912: 137-143
  • 22 Kallberg ME, Brooks DE, Gelatt KN. et al. Endothelin-1, nitric oxide, and glutamate in the normal and glaucomatous dog eye. Vet Ophthalmol 2007; 10 (Suppl. 01) S46-S52 doi:10.1111/j.1463-5224.2007.00529.x
  • 23 Kawanabe Y, Nauli SM. Involvement of extracellular Ca2+ influx through voltage-independent Ca2+ channels in endothelin-1 function. Cell Signal 2005; 17: 911-916 doi:10.1016/j.cellsig.2005.01.001
  • 24 Pollock DM, Keith TL, Highsmith RF. Endothelin receptors and calcium signaling. FASEB J 1995; 9: 1196-1204
  • 25 Shetty SS, Okada T, Webb RL. et al. Functionally distinct endothelin B receptors in vascular endothelium and smooth muscle. Biochem Biophys Res Commun 1993; 191: 459-464 doi:10.1006/bbrc.1993.1240
  • 26 Yao K, Tschudi M, Flammer J. et al. Endothelium-dependent regulation of vascular tone of the porcine ophthalmic artery. Invest Ophthalmol Vis Sci 1991; 32: 1791-1798
  • 27 Haefliger IO, Flammer J, Lüscher TF. Nitric oxide and endothelin-1 are important regulators of human ophthalmic artery. Invest Ophthalmol Vis Sci 1992; 33: 2340-2343
  • 28 Haefliger IO, Flammer J, Lüscher TF. Heterogeneity of endothelium-dependent regulation in ophthalmic and ciliary arteries. Invest Ophthalmol Vis Sci 1993; 34: 1722-1730
  • 29 Meyer P, Flammer J, Lüscher TF. Endothelium-dependent regulation of the ophthalmic microcirculation in the perfused porcine eye: role of nitric oxide and endothelins. Invest Ophthalmol Vis Sci 1993; 34: 3614-3621
  • 30 Haefliger IO, Meyer P, Flammer J. et al. The vascular endothelium as a regulator of the ocular circulation: a new concept in ophthalmology?. Surv Ophthalmol 1994; 39: 123-132
  • 31 Flammer J. The vascular concept of glaucoma. Surv Ophthalmol 1994; 38 (Suppl.) S3-S6
  • 32 Schmetterer L, Findl O, Strenn K. et al. Effects of endothelin-1 (ET-1) on ocular hemodynamics. Curr Eye Res 1997; 16: 687-692
  • 33 Ciulla TA, Pawlyk BS, Harris A. et al. Endothelin-1-mediated retinal artery vasospasm and the rabbit electroretinogram. J Ocul Pharmacol Ther 2000; 16: 393-398 doi:10.1089/jop.2000.16.393
  • 34 Konieczka K, Ritch R, Traverso CE. et al. Flammer syndrome. EPMA J 2014; 5: 11 doi:10.1186/1878-5085-5-11
  • 35 Flammer J, Konieczka K. The discovery of the Flammer syndrome: a historical and personal perspective. EPMA J 2017; 8: 75-97 doi:10.1007/s13167-017-0090-x
  • 36 Cioffi GA, Orgül S, Onda E. et al. An in vivo model of chronic optic nerve ischemia: the dose-dependent effects of endothelin-1 on the optic nerve microvasculature. Curr Eye Res 1995; 14: 1147-1153
  • 37 Orgül S, Cioffi GA, Bacon DR. et al. An endothelin-1-induced model of chronic optic nerve ischemia in rhesus monkeys. J Glaucoma 1996; 5: 135-138
  • 38 Orgül S, Cioffi GA, Wilson DJ. et al. An endothelin-1 induced model of optic nerve ischemia in the rabbit. Invest Ophthalmol Vis Sci 1996; 37: 1860-1869
  • 39 Emre M, Orgül S, Haufschild T. et al. Increased plasma endothelin-1 levels in patients with progressive open angle glaucoma. Br J Ophthalmol 2005; 89: 60-63
  • 40 McGrady NR, Minton AZ, Stankowska DL. et al. Upregulation of the endothelin A (ETA) receptor and its association with neurodegeneration in a rodent model of glaucoma. BMC Neurosci 2017; 18: 27 doi:10.1186/s12868-017-0346-3
  • 41 Sugiyama K, Haque MS, Okada K. et al. Intraocular pressure response to intravitreal injection of endothelin-1 and the mediatory role of ETA receptor, ETB receptor, and cyclooxygenase products in rabbits. Curr Eye Res 1995; 14: 479-486
  • 42 Granstam E, Wang L, Bill A. Effects of endothelins (ET-1, ET-2 and ET-3) in the rabbit eye; role of prostaglandins. Eur J Pharmacol 1991; 194: 217-223
  • 43 Holló G, Kóthy P, Lakatos P. et al. Endothelin-A receptor antagonist BQ-485 protects against intraocular pressure spike induced by laser trabeculoplasty in the rabbit. Ophthalmologica 2002; 216: 459-462
  • 44 Holló G, Lakatos P, Vargha P. Immediate increase in aqueous humour endothelin 1 concentration and intra-ocular pressure after argon laser trabeculoplasty in the rabbit. Ophthalmologica 2000; 214: 292-295
  • 45 Holló G, Visontai Z, Lakatos P. et al. Unoprostone isopropyl pretreatment decreases endothelin-1 release and the intra-ocular pressure spike induced by laser trabeculoplasty in the rabbit. Ophthalmologica 2003; 217: 231-236
  • 46 Nonoyama T, Takei K, Sato T. et al. [The effect of subconjunctival injection of endothelin-1 on intraocular pressure in the rabbit]. Nippon Ganka Gakkai Zasshi 1995; 99: 1133-1139
  • 47 Wiederholt M. Direct involvement of trabecular meshwork in the regulation of aqueous humor outflow. Curr Opin Ophthalmol 1998; 9: 46-49
  • 48 Wiederholt M, Haefliger IO, Flammer J. Nitric Oxide and Endothelin in aqueous Humor Outflow Regulation. In: Haefliger IO, Flammer J. eds. Nitric Oxide and Endothelin in the Pathogenesis of Glaucoma. Philadelphia: Lippincott-Raven Publishers; 1998: 168-177
  • 49 Choritz L, Rosenthal R, Fromm M. et al. Pharmacological and functional characterization of endothelin receptors in bovine trabecular meshwork and ciliary muscle. Ophthalmic Res 2005; 37: 179-187 doi:10.1159/000086471
  • 50 Chen HY, Chang YC, Chen WC. et al. Association between plasma endothelin-1 and severity of different types of glaucoma. J Glaucoma 2013; 22: 117-122 doi:10.1097/IJG.0b013e31822e8c65
  • 51 Choritz L, Machert M, Thieme H. Correlation of endothelin-1 concentration in aqueous humor with intraocular pressure in primary open angle and pseudoexfoliation glaucoma. Invest Ophthalmol Vis Sci 2012; 53: 7336-7342 doi:10.1167/iovs.12-10216
  • 52 Battistelli S, Gori S, Borgogni T. et al. [Variation in the plasma endothelin levels in relation to age]. Minerva Cardioangiol 1996; 44: 111-114
  • 53 Komatsumoto S, Nara M. [Changes in the level of endothelin-1 with aging]. Nihon Ronen Igakkai Zasshi 1995; 32: 664-669
  • 54 Li S, Zhang A, Cao W. et al. Elevated plasma endothelin-1 levels in normal tension glaucoma and primary open-angle glaucoma: a meta-analysis. J Ophthalmol 2016; 2016: 2678017 doi:10.1155/2016/2678017
  • 55 Lopez-Riquelme N, Villalba C, Tormo C. et al. Endothelin-1 levels and biomarkers of oxidative stress in glaucoma patients. Int Ophthalmol 2015; 35: 527-532 doi:10.1007/s10792-014-9979-8
  • 56 Lee NY, Park HY, Park CK. et al. Analysis of systemic endothelin-1, matrix metalloproteinase-9, macrophage chemoattractant protein-1, and high-sensitivity C-reactive protein in normal-tension glaucoma. Curr Eye Res 2012; 37: 1121-1126 doi:10.3109/02713683.2012.725798
  • 57 Kaiser HJ, Flammer J, Wenk M. et al. Endothelin-1 plasma levels in normal-tension glaucoma: abnormal response to postural changes. Graefes Arch Clin Exp Ophthalmol 1995; 233: 484-488
  • 58 Buckley C, Hadoke PW, Henry E. et al. Systemic vascular endothelial cell dysfunction in normal pressure glaucoma. Br J Ophthalmol 2002; 86: 227-232
  • 59 Nützi C, Schötzau A, Grieshaber MC. Structure and function relationship of activated retinal glia in primary open-angle glaucoma patients. J Ophthalmol 2017; 2017: 7043752 doi:10.1155/2017/7043752
  • 60 Grieshaber MC, Moramarco F, Schoetzau A. et al. Detection of retinal glial cell activation in glaucoma by time domain optical coherence tomography. Klin Monatsbl Augenheilkd 2012; 229: 314-318 doi:10.1055/s-0031-1281857
  • 61 Grieshaber MC, Orgul S, Schoetzau A. et al. Relationship between retinal glial cell activation in glaucoma and vascular dysregulation. J Glaucoma 2007; 16: 215-219 doi:10.1097/IJG.0b013e31802d045a
  • 62 Prasanna G, Krishnamoorthy R, Yorio T. Endothelin, astrocytes and glaucoma. Exp Eye Res 2011; 93: 170-177 doi:10.1016/j.exer.2010.09.006
  • 63 Rao VR, Krishnamoorthy RR, Yorio T. Endothelin-1 mediated regulation of extracellular matrix collagens in cells of human lamina cribrosa. Exp Eye Res 2008; 86: 886-894 doi:10.1016/j.exer.2008.03.003
  • 64 Yorio T, Krishnamoorthy R, Prasanna G. Endothelin: is it a contributor to glaucoma pathophysiology?. J Glaucoma 2002; 11: 259-270
  • 65 Lee NY, Park HY, Na KS. et al. Association between heart rate variability and systemic endothelin-1 concentration in normal-tension glaucoma. Curr Eye Res 2013; 38: 516-519 doi:10.3109/02713683.2012.745881
  • 66 Kosior-Jarecka E, Wrobel-Dudzinska D, Lukasik U. et al. Plasma endothelin-1 and single nucleotide polymorphisms of endothelin-1 and endothelin type A receptor genes as risk factors for normal tension glaucoma. Mol Vis 2016; 22: 1256-1266
  • 67 Wrobel-Dudzinska D, Kosior-Jarecka E, Lukasik U. et al. Risk factors in normal-tension glaucoma and high-tension glaucoma in relation to polymorphisms of endothelin-1 gene and endothelin-1 receptor type a gene. J Ophthalmol 2015; 2015: 368792 doi:10.1155/2015/368792
  • 68 Flammer J, Konieczka K. Retinal venous pressure: the role of endothelin. EPMA J 2015; 6: 21 doi:10.1186/s13167-015-0043-1
  • 69 Meyer P, Lang MG, Flammer J. et al. Effects of calcium channel blockers on the response to endothelin-1, bradykinin and sodium nitroprusside in porcine ciliary arteries. Exp Eye Res 1995; 60: 505-510
  • 70 Strenn K, Matulla B, Wolzt M. et al. Reversal of endothelin-1-induced ocular hemodynamic effects by low-dose nifedipine in humans. Clin Pharmacol Ther 1998; 63: 54-63
  • 71 Fang L, Turtschi S, Mozaffarieh M. The effect of nifedipine on retinal venous pressure of glaucoma patients with the Flammer-syndrome. Graefes Arch Clin Exp Ophthalmol 2015; 253: 935-939 doi:10.1007/s00417-015-3001-7
  • 72 Rosenthal R, Fromm M. Endothelin antagonism as an active principle for glaucoma therapy. Br J Pharmacol 2011; 162: 806-816 doi:10.1111/j.1476-5381.2010.01103.x
  • 73 Baynash AG, Hosoda K, Giaid A. et al. Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons. Cell 1994; 79: 1277-1285
  • 74 Resch H, Karl K, Weigert G. et al. Effect of dual endothelin receptor blockade on ocular blood flow in patients with glaucoma and healthy subjects. Invest Ophthalmol Vis Sci 2009; 50: 358-363
  • 75 Neumann T, Baertschi M, Vilser W. et al. Retinal vessel regulation at high altitudes1. Clin Hemorheol Microcirc 2016; 63: 281-292 doi:10.3233/CH-162041