Zusammenfassung
Dem Pseudoexfoliations(PEX)-Glaukom, der mit Abstand wichtigsten und häufigsten Form
der Sekundärglaukome, liegt ein generalisierter, genetisch determinierter, elastotischer
Matrixprozess als identifizierbare Glaukomursache zugrunde. Er ist charakterisiert
durch die exzessive Produktion und progressive Ablagerung eines fibrillären extrazellulären
Materials in verschiedenen Geweben einschließlich der Kammerwasserabflusswege. Eine
wachsende Datenlage scheint zu bestätigen, dass die oxidative-antioxidative Balance
bei Patienten mit PEX-Syndrom und PEX-Glaukom, sowohl im vorderen Augenabschnitt als
auch systemisch, gestört ist und dass der daraus resultierende oxidative Stress eine
zentrale Rolle in der Pathogenese des abnormalen Matrixprozesses spielt. Störungen
der antioxidativen Schutzmechanismen umfassen erniedrigte Konzentrationen von Ascorbinsäure,
Glutathion, antioxidativen Spurenelementen und verschiedenen antioxidativen Enzymen,
welche auch eine Dysregulation auf mRNA-Ebene in PEX-Geweben zeigen. Als weitere Hinweise
auf das Vorliegen von oxidativem Stress dienen erhöhte Konzentrationen von Oxidantien,
wie Wasserstoffperoxid und Stickstoffmonoxid, und oxidativer Stressmarker, wie Lipidperoxidationsprodukte,
Abbauprodukte oxidierter und methylierter Proteine, Advanced Glycation End Products
und Homocystein in Kammerwasser, Serum und okulären Geweben. Grundlagenforschungen
konnten weiterhin zeigen, dass chronischer oxidativer Stress, zusammen mit unzureichenden
zellulären Schutz- und Reparaturmechanismen, den aberranten Matrixmetabolismus durch
Induktion einer anhaltenden subklinischen Entzündungsreaktion und Aktivierung des
profibrotischen Wachstumsfaktors TGF-β1 entscheidend beeinflussen kann. Oxidativer
Stress scheint demnach einen modifizierbaren Risikofaktor in der Behandlung von Patienten
mit PEX-Syndrom/Glaukom darzustellen.
Abstract
Pseudoexfoliation (PEX) glaucoma is the most common identifiable cause of open-angle
glaucoma worldwide, comprising the majority of glaucoma in some countries. The underlying
disorder, PEX syndrome, is a generalised, genetically determined, elastotic process
of the extracellular matrix characterised by the excessive production and progressive
accumulation of a fibrillar material in various tissues including the outflow pathways.
Increasing evidence suggests that the oxidative-antioxidative balance is disturbed
in patients with PEX syndrome/glaucoma, both in the anterior segment and throughout
the body, and that the resulting oxidative stress constitutes a major mechanism involved
in the pathophysiology of this fibrotic process. Significantly reduced levels of antioxidants,
such as ascorbic acid, glutathione, trace elements, antioxidative enzymes, and total
antioxidative capacity in aqueous humor and serum suggest a faulty antioxidative defense
system in PEX patients. The down-regulation of antioxidative enzymes in anterior segment
tissues also indicates an inadequate cytoprotection against oxidative stress. Concomitantly,
levels of oxidants such as hydrogen peroxide or nitric oxide, and oxidative stress
markers, including lipid peroxidation products, degradation products of oxidated and
methylated proteins, advanced glycation end products, and homocysteine are significantly
increased in aqueous humor, tissues, and serum. The available data suggest that chronic
oxidative stress in combination with weakened cytoprotective and repair strategies
affects the abnormal matrix metabolism by induction of a persistent pro-inflammatory
state and activation of the profibrotic growth factor TGF-β1. Oxidative stress, therefore,
appears to represent a modifiable risk factor in the management of patients with PEX
syndrome/glaucoma.
Schlüsselwörter
Pseudoexfoliationssyndrom - PEX-Glaukom - oxidativer Stress - extrazelluläre Matrix
- TGF-ß1
Key words
pseudoexfoliation syndrome - pseudoexfoliation glaucoma - oxidative stress - extracellular
matrix - TGF-ß1
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Prof. Dr. Ursula Schlötzer-Schrehardt
Augenklinik, Universität Erlangen-Nürnberg
Schwabachanlage 6
91054 Erlangen
Telefon: ++ 49/91 31/8 53 44 33
Fax: ++ 49/91 31/8 53 46 31
eMail: ursula.schloetzer@augen.imed.uni-erlangen.de
