Oxidativer Stress im Trabekelwerk beim POWG

Zusammenfassung

Das primäre Offenwinkelglaukom (POWG) wird als eine Optikusneuropathie definiert, bei der es zu einem Verlust von Axonen des Nervus opticus und der dazugehörigen Ganglienzellen kommt. Die Ursache dieser Schädigung ist bis heute nicht geklärt. In der Pathogenese und Progression des POWG werden verschiedene Faktoren wie ein erhöhter intraokulärer Druck und eine verminderte okuläre Durchblutung verantwortlich gemacht. Aus morphologischen Untersuchungen ist bekannt, dass die Druckerhöhung beim POWG auf einer Erhöhung des Abflusswiderstandes im Bereich des Trabekelwerkes beruht. Das Trabekelwerk (TW) des POWG-Patienten zeichnet sich unter anderem durch folgende spezifische morphologische und biochemische Veränderungen aus: Akkumulation von extrazellulärer Matrix, beschleunigte Alterung, Apoptose, subklinische chronische Entzündungen und Veränderungen im Zytoskelett. Die Ursache und die Vorgänge, die zu diesen Veränderungen führen, sind bis heute nicht geklärt. In der Pathogenese des POWG wird zunehmend oxidativer Stress diskutiert. Wissenschaftliche Untersuchungen deuten darauf hin, dass im TW von POWG-Patienten ein vermehrter oxidativer Stress vorliegt. Die Behandlung von kultivierten TW-Zellen führt zu den genannten glaukomtypischen Veränderungen. Durch die Vorbehandlung mit Antioxidantien aber auch mit Wirkstoffen von modernen Antiglaukomatosa können diese glaukomtypischen Veränderungen in TW reduziert werden. Zusammenfassend können in vitro POWG-typische Veränderungen im TW durch oxidativen Stress induziert werden. Somit könnte eine Reduktion des oxidativen Stresses im TW ein wirkungsvoller Ansatz sein, die Progression des POWG zu reduzieren.

Abstract

Primary open angle glaucoma (POAG) is defined as an optic neuropathy which is characterised by the loss of optic nerve axons and the related retinal ganglion cells. The reason for these changes is still unknown. In the pathogenesis of POAG several factors like increased intraocular pressure and a reduction of ocular blood supply are discussed. Morphological and biochemical analyses of the trabecular meshwork (TM) of POAG patients revealed loss of cells, increased accumulation of extracellular matrix (ECM), changes in the cytoskeleton, cellular senescence and the process of subclinical inflammation. One factor becoming more likely to be involved in the pathogenesis of POAG is oxidative stress. Treatment of TM cells with oxidative stress induced POAG-typical changes like ECM accumulation, cell death, disarrangement of the cytoskeleton, advanced senescence and the release of inflammatory markers. By pretreatment with antioxidants, prostaglandin analogues, beta-blockers or local carbonic anhydrase inhibitors, these effects were markedly reduced. In conclusion, oxidative stress is able to induce characteristic glaucomatous TM changes in vitro and these oxidative stress-induced TM changes can be minimised by the use of antioxidants and IOP-lowering substances. It is tempting to speculate that prevention of oxidative stress exposure to the TM may help to reduce the progression of POAG.

Schlüsselwörter

Glaukom - oxidativer Stress - Trabekelwerk

Key words

glaucoma - oxidative stress - trabecular meshwork

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