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Mechanismen der Neuroprotektion bei Glaukomen

Mechanisms of neuroprotection against glaucoma

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Zusammenfassung

Das Ziel der Neuroprotektion in der Glaukomtherapie ist der Einsatz von Wirkstoffen, die die Apoptose der retinalen Ganglienzellen (RGZ) verhindern bzw. verzögern und die Regeneration bereits geschädigter Zellen fördern. Im folgenden Beitrag werden die Mechanismen des Zelluntergangs der RGZ und der Stand der neuroprotektiven In-vivo-Studien sowie Untersuchungen an Zellkulturen und im Tierversuch erörtert. In der Ätiopathogenese des primär chronischen Offenwinkelglaukoms (PCOWG) werden vor allem ein erhöhter IOD und vaskuläre Funtionsstörungen am Auge diskutiert. Weiterhin werden die Mechanismen der axonschädigenden Wirkung der Ischämie erläutert und hieraus resultierende mögliche neuroprotektive Wirkmechanismen dargestellt (Na+- bzw. Ca2+-Kanalblocker, Rolle reaktiver Astrozyten). Der Ersatz axonaler Überlebensfaktoren und hier besonders die Rolle des im Gehirn gebildeten neurotrophen Faktors werden beschrieben. Ebenso spielt die Glutamatexzitotoxizität eine Rolle im glaukomatösen, anterograden RGZ-Untergang. Hiermit zusammenhängende Fragestellungen und mögliche Therapieansätze werden erörtert. Die drei Phasen der Apoptosekaskade und die Schlüsselrolle der Mitochondrien bei der insultinduzierten Apoptose werden ebenso berücksichtigt, wie die noch relativ unerforschte Möglichkeit der RGZ-Regeneration. Schlussendlich werden Perspektiven der neuroprotektiven Therapie bei PCOWG dargelegt.

Abstract

The goal of neuroprotection in glaucoma treatment is to employ agents that prevent or delay apoptosis of retinal ganglion cells (RGC) and facilitate regeneration of already damaged calls. The following contribution discusses the mechanisms of RGC death and current status of neuroprotective in vivo studies and investigations on cell cultures and animal models. Discussions on the etiopathogenesis of PCOAG center on elevated IOP and ocular disorders of vascular function. The mechanisms of axonal damage induced by ischemia are explained and the resultant possible neuroprotective effect mechanisms are discussed (Na+ or Ca2+ channel blockers, role of reactive astrocytes). Substitution of axonal survival factors and especially the role of BDNF are described. Glutamate excitotoxicity also plays a role in glaucomatous antegrade RGC death. Relevant questions and possible therapeutic approaches are discussed. The three phases of apoptosis cascade and the key role of mitochondria in the insult-induced apoptosis are considered as well as the still relatively unexplored possibilities of RGC regeneration. Finally, perspectives of neuroprotective treatment of PCOAG are presented.

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  1. Mount Sinai School of Medicine, New York, NY, USA

    T. Mittag

  2. Augenklinik, Universität, Dresden

    K.-G. Schmidt

  3. Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA

    T. Mittag

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Mittag, T., Schmidt, KG. Mechanismen der Neuroprotektion bei Glaukomen. Ophthalmologe 101, 1076–1086 (2004). https://doi.org/10.1007/s00347-004-1130-1

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