Skip to main content
SpringerLink
Log in

Funktionelle Bedeutung der Adenosinrezeptoren im Auge und ihre Dysregulation beim Pseudoexfoliationssyndrom

Functional significance of adenosine receptors in the eye and their dysregulation in pseudoexfoliation syndrome

  • Originalien
  • Published:
Der Ophthalmologe Aims and scope Submit manuscript

Zusammenfassung

Hintergrund

Adenosin reguliert durch die Aktivierung seiner Rezeptoren zahlreiche physiologische Prozesse, z. B. eine Zytoprotektion bei Ischämie/Hypoxie sowie die Kammerwassersekretion und damit den Augeninnendruck. Wir untersuchten die Expression der Rezeptorisoformen in Augen mit PEX-Syndrom, das mit einer ausgeprägten Vorderkammerhypoxie und erhöhtem Augeninnendruck assoziiert ist.

Material und Methoden

Die mRNA- und Proteinexpression der Adenosinrezeptorsubtypen in okulären Geweben von Patienten mit PEX-Syndrom, Glaukomen und normalen Augen wurden vergleichend analysiert.

Ergebnisse

Während die Rezeptorsubtypen A1, A2a und A2b keine Expressionsunterschiede zwischen PEX- und Kontrollgeweben zeigten, war die Expression des A3-Adenosinrezeptors im unpigmentierten Ziliarepithel aller PEX-Augen, unabhängig vom Vorhandensein eines Glaukoms, im Vergleich mit normalen und glaukomatösen Kontrollaugen signifikant erhöht.

Schlussfolgerung

Die in der Vorderkammer von PEX-Augen vorliegenden Stressbedingungen scheinen zu einer selektiven Induktion der A3-Rezeptorexpression im Ziliarepithel zu führen. Der A3-Adenosinrezeptor könnte als potenzielles Targetmolekül für neue Therapieansätze bei PEX-Patienten dienen.

Abstract

Background

Adenosine regulates many physiologic processes, such as aqueous humor secretion and intraocular pressure, via activation of its receptors. We investigated the expression of the receptor isoforms in eyes with PEX syndrome, which is associated with anterior chamber hypoxia and elevated intraocular pressure.

Materials and methods

The mRNA and protein expression of the adenosine receptor subtypes in anterior segment tissues of patients with PEX syndrome, glaucomas, and normal control eyes were analyzed comparatively.

Results

Whereas the receptor subtypes A1, A2a, and A2b displayed no differential expression between PEX and control tissues, expression of the A3 adenosine receptor was consistently enhanced in the nonpigmented ciliary epithelium of all PEX eyes, independent of the presence of glaucoma, compared to normal and glaucomatous control eyes.

Conclusion

Considering the known role of the A3 adenosine receptor in modulating aqueous humor secretion, its selective upregulation in the ciliary epithelium may confer cytoprotection and be accessible to therapeutic intervention in PEX patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3
Abb. 4
Abb. 5
Abb. 6

Literatur

  1. Avila MY, Stone RA, Civan MM (2001) A1-, A2A- and A3-subtype adenosine receptors modulate intraocular pressure in the mouse. Br J Pharmacol 134: 241–245

    Google Scholar 

  2. Avila MY, Stone RA, Civan MM (2002) Knockout of A3 adenosine receptors reduces mouse intraocular pressure. Invest Ophthalmol Vis Sci 43: 3021–3026

    Google Scholar 

  3. Braunagel SC, Xiao JG, Chiou GC (1988) The potential role of adenosine in regulating blood flow in the eye. J Ocular Pharm 4: 61–73

    Google Scholar 

  4. Bruns RF (1990) Adenosine receptors: roles and pharmacology. Ann NY Acad Sci 603: 211–225

    Google Scholar 

  5. Carre DA, Mitchell CH, Peterson-Yantorno K, Coca-Prados M, Civan MM (1997) Adenosine stimulates Cl− channels of nonpigmented ciliary epithelial cells. Am J Physiol 273: C1354–C1361

    Google Scholar 

  6. Civan MM (2003) The fall and rise of active chloride transport: implications for regulation of intraocular pressure. J Exp Zool 300A: 5–13

    Google Scholar 

  7. Crosson CE (1995) Adenosine receptor activation modulates intraocular pressure in rabbits. J Pharmacol Exp Ther 273: 320–326

    Google Scholar 

  8. Crosson CE, Gray T (1996) Characterization of ocular hypertension induced by adenosine agonists. Invest Ophthalmol Vis Sci 37: 1833–1839

    Google Scholar 

  9. Daines BS, Kent AR, McAleer MS, Crosson CE (2003) Intraocular adenosine levels in normal and ocular hypertensive patients. J Ocular Pharmacol Ther 19: 113–119

    Google Scholar 

  10. Fleischhauer JC, Mitchell CH, Stamer WD, Karl MO, Peterson-Yantorno K, Civan MM (2003) Common actions of adenosine receptor agonists in modulating human trabecular meshwork cell transport. J Membr Biol 193: 121–136

    Google Scholar 

  11. Fredholm BB, Ijzerman AP, Jacobson KA, Klotz K-N, Linden J (2001) Nomenclature and classification of adenosine receptors. Pharm Rev 53: 527–552

    Google Scholar 

  12. Gregory CY, Abrams TA, Hall MO (1994) Stimulation of A2 adenosine receptors inhibits the ingestion of photoreceptor outer segments by retinal pigment epithelium. Invest Ophthalmol Vis Sci 35: 819–825

    Google Scholar 

  13. Helbig H, Schlötzer-Schrehardt U, Noske W, Kellner U, Foerster MH, Naumann GO (1994) Anterior-chamber hypoxia and iris vasculopathy in pseudoexfoliation syndrome. German J Ophthalmol 3: 148–153

    Google Scholar 

  14. Johnson DH, Brubaker RF (1982) Dynamics of aqueous humor in the syndrome of exfoliation with glaucoma. Am J Ophthalmol 93: 629–634

    Google Scholar 

  15. Koliakos GG, Konstas AG, Schlötzer-Schrehardt U, Hollo G, Katsimbris IE, Georgiadis N, Ritch R (2003) 8-isoprostaglandin F2A and ascorbic acid concentration in the aqueous humour of patients with exfoliation syndrome. Br J Ophthalmol 87: 353–356

    Google Scholar 

  16. Kvanta A, Seregard S, Sejersen S, Kull B, Fredholm BB (1997) Localization of adenosine receptor messenger RNAs in the rat eye. Exp Eye Res 65: 595–602

    Google Scholar 

  17. Larsen AK, Osbourne NN (1996) Involvement of adenosine in retinal ischemia. Studies on rat. Invest Ophthalmol Vis Sci 37: 2603–2611

    Google Scholar 

  18. Lutty GA, McLeod DS (2003) Retinal vascular development and oxygen-induced retinopathy: a role for adenosine. Progr Ret Eye Res 22: 95–111

    Google Scholar 

  19. Macaluso C, Frishman LJ, Frueh B, Kaelin-Lang A, Onoe S, Niemeyer G (2003) Multiple effects of adenosine in the arterially perfused mammalian eye. Possible mechanisms for the neuroprotective function of adenosine in the retina. Doc Ophthalmol 106: 51–59

    Google Scholar 

  20. Mitchell CH, Peterson-Yantorno K, Carre DA, McGlinn AM, Coca-Prados M, Stone RA, Civan MM (1999) A3 adenosine receptors regulate Cl− channels of nonpigmented ciliary epithelial cells. Am J Physiol 276: C659–C666

    Google Scholar 

  21. Naumann GO, Schlötzer-Schrehardt U, Küchle M (1998) Pseudoexfoliation syndrome for the comprehensive ophthalmologist. Intraocular and systemic manifestations. Ophthalmology 105: 951–968

    Google Scholar 

  22. Okamura T, Kurogi Y, Hashimoto K, Sato S, Nishikawa H, Kiryu K, Nagao Y (2004) Structure-activity relationships of adenosine A3 receptor ligands: new potential therapy for the treatment of glaucoma. Bioorg Med Chem Lett 14: 3775–3779

    Google Scholar 

  23. Polska E, Ehrlich P, Luksch AQ, Fuchsjäger-Mayrl G, Schmetterer L (2003) Effects of adenosine on intraocular pressure, optic nerve head blood flow, and choroidal blood flow in healthy humans. Invest Ophthalmol Vis Sci 44: 3110–3114

    Google Scholar 

  24. Portellos M, Riva CE, Cranstoun SD, Petrig BL, Brucker AJ (1995) Effects of adenosine on ocular blood flow. Invest Ophthalmol Vis Sci 36: 1904–1909

    Google Scholar 

  25. Ramkumar V, Hallam DM, Nie Z (2001) Adenosine, oxidative stress and cytoprotection. Jpn J Pharmacol 86: 265–274

    Google Scholar 

  26. Riley MV, Winkler BS, Starnes CA, Peters MI (1996) Adenosine promotes regulation of corneal hydration through cyclic adenosine monophosphate. Invest Ophthalmol Vis Sci 37: 1–10

    Google Scholar 

  27. Roth S, Rosenbaum PS, Osinski J, Park SS, Toledano AY, Li B, Moshfeghi AA (1997) Ischemia induces significant changes in purine nucleoside concentration in the retina-choroid in rats. Exp Eye Res 65: 771–779

    Google Scholar 

  28. Schlötzer-Schrehardt U, Zenkel M, Hofmann-Rummelt C, Naumann GO (2004) The A3 adenosine receptor is upregulated in eyes with pseudoexfoliation syndrome and glaucoma. Invest Ophthalmol Vis Sci 45: E-Abstract 3535

    Google Scholar 

  29. Sen HA, Campochiaro PA (1989) Intravitreous injection of adenosine or its agonists causes breakdown of the blood-retinal barrier. Arch Ophthalmol 107: 1364–1367

    Google Scholar 

  30. Tian B, Gabelt BT, Crosson CE, Kaufman PL (1997) Effects of adenosine agonists on intraocular pressure and aqueous humor dynamics in cynomolgus monkeys. Exp Eye Res 64: 979–989

    Google Scholar 

  31. Wax M, Sanghavi DM, Lee CH, Kapadia M (1993) Purinergic receptors in ocular ciliary epithelial cells. Exp Eye Res 57: 89–95

    Google Scholar 

Download references

Interessenkonflikt:

Der korrespondierende Autor versichert, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen.

Author information

Authors and Affiliations

  1. Augenklinik der Friedrich-Alexander-Universität Erlangen-Nürnberg

    U. Schlötzer-Schrehardt, M. Zenkel, C. Hofmann-Rummelt, F. E. Kruse & G. O. Naumann

  2. Augenklinik, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen

    U. Schlötzer-Schrehardt

Authors
  1. U. Schlötzer-Schrehardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Zenkel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Hofmann-Rummelt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F. E. Kruse
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. O. Naumann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to U. Schlötzer-Schrehardt.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schlötzer-Schrehardt, U., Zenkel, M., Hofmann-Rummelt, C. et al. Funktionelle Bedeutung der Adenosinrezeptoren im Auge und ihre Dysregulation beim Pseudoexfoliationssyndrom. Ophthalmologe 102, 1074–1082 (2005). https://doi.org/10.1007/s00347-005-1216-4

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00347-005-1216-4

Schlüsselwörter

Keywords

Search

Navigation