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Besonderheiten der Optikusganglienzellen und Ansätze zur Neuroprotektion

Von intrazellulären Vorgängen zur Kapillare bis zu therapeutischen Überlegungen

Characteristic features of optic nerve ganglion cells and approaches for neuroprotection

From intracellular to capillary processes and therapeutic considerations

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Zusammenfassung

Bei vielen Erkrankungen, die mit einer Verschlechterung des Gesichtsfelds und des Sehvermögens einhergehen, sind die Optikusganglienzellen am stärksten gefährdet. Auch beim PCOWG wird der Krankheitsverlauf von dem Grad ihrer Beschädigung bestimmt. Aufgrund ihrer Anatomie sind sie großen metabolischen und mikrozirkulationsbedingten Belastungen unterworfen. So führt das Zusammenspiel von Hypoxie und metabolischer Belastung zur Schädigung retinaler Ganglienzellen. Hinzu kommt oxidativer Stress und eine altersabhängige Vermehrung von „Advanced glycation endproducts“. Im folgenden Beitrag werden Überlegungen zur Verzögerung des Ganglienzelltods—beispielsweise durch Neuroprotektiva—bei PCOWG angestellt. Des Weiteren könnten Wirkstoffe, die den Kalziuminflux in die Zelle reduzieren, den Zelluntergang verhindern. Ebenso könnten Antagonisten des NMDA-Rezeptors wirken, hierbei sind allerdings erhebliche Nebenwirkungen zu befürchten. Auch Antioxidanzien wird bei der Bekämpfung des PCOWG in Form der Verhinderung der Apoptose eine theoretische Bedeutung zugesprochen. Letztlich sollte das ideale Glaukommedikament gut per os verträglich sein, den Untergang retinaler Ganglienzellen verhindern und ein geringes Nebenwirkungsprofil besitzen.

Abstract

In many diseases associated with deterioration of the visual field and eyesight, optic nerve ganglion cells are at the highest risk. The clinical course of primary chronic open-angle glaucoma (PCOAG) is also determined by the degree of damage to these cells. Due to their anatomy, they are subject to extreme stress exerted by metabolic and microcirculatory forces. The interaction between hypoxia and metabolic stress leads to damage of the retinal ganglion cells. This is compounded by oxidative stress and age-dependent increase of advanced glycation end products. The following contribution gives consideration to approaches for delaying ganglion cell death in PCOAG, e.g., with neuroprotective agents. Furthermore, agents that reduce calcium influx into the cells could prevent cell destruction. Likewise, NMDA receptor antagonists could be effective; however, considerable side effects are to be feared. Antioxidants are also attributed with theoretical impact in combating PCOAG by preventing apoptosis. Finally, the ideal glaucoma medication should be well tolerated when taken orally, prevent destruction of retinal ganglion cells, and possess a low side effect profile.

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Funk, R.H.W., Schmidt, KG. Besonderheiten der Optikusganglienzellen und Ansätze zur Neuroprotektion. Ophthalmologe 101, 1062–1070 (2004). https://doi.org/10.1007/s00347-004-1116-z

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