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Klin Monbl Augenheilkd 2013; 230(2): 114-119
DOI: 10.1055/s-0032-1327825
Übersicht
Georg Thieme Verlag KG Stuttgart · New York

Stellenwert der „nicht Augendruck senkenden Glaukomtherapie“

Value of Non-IOP Lowering Therapy for Glaucoma
A. Cybulska-Heinrich
Department of Ophthalmology, University of Basel, Switzerland
,
M. Mozaffarieh
Department of Ophthalmology, University of Basel, Switzerland
,
J. Flammer
Department of Ophthalmology, University of Basel, Switzerland
› Author Affiliations
Further Information

Publication History

eingereicht 30 August 2012

akzeptiert 11 September 2012

Publication Date:
21 February 2013 (online)

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Zusammenfassung

Es ist schon lange bekannt, dass ein erhöhter Augendruck Ursache für das Glaukom ist. Somit konzentriert sich auch die klassische Glaukomtherapie auf die Senkung des Augeninnendrucks (IOD). Dies hat nun, da es oft nicht ausreicht und es bei mäßigem oder normalem Augendruck zu Schäden kommen kann, das Bedürfnis nach neuen therapeutischen Ansätzen eröffnet. Es müssen auch andere Risikofaktoren (außer des Augendrucks) für den Glaukomschaden mitverantwortlich sein, die man behandeln sollte. Ein solcher Risikofaktor ist z.B die gestörte Regulation der Durchblutung. Wenn der Augendruck oder der Blutdruck schwankt, kann das Auge normalerweise die Durchblutung durch Selbstregulation konstant halten. Ist diese Regulierung gestört, kommt es zu einer instabilen Sauerstoffversorgung, was zu oxidativem Stress und somit zum Glaukomschaden führt. Während sich einige dieser Therapien noch in der experimentellen Phase befinden, werden andere bereits im klinischen Alltag eingesetzt.

Eine primäre vaskuläre Dysregulation (PVD) und die daraus resultierende, veränderte Autoregulation in der Augendurchblutung (OBF) können mit Magnesium und – bei ausbleibendem Effekt – mit niedrig dosierten Kalziumantagonisten besser behandelt werden. Starke nächtliche Blutdruckabfälle können anfangs durch erhöhte Salz- und Flüssigkeitsaufnahme und – falls das nicht genügt – in einem weiteren Schritt mit Fludrocortison vermieden werden. Oxidativer Stress (bedingt durch instabile Sauerstoffversorgung) sollte mit Nahrungsmitteln mit antioxidativer Wirkung, die reich an Polyphenol-Flavonoiden (wie Tee, Kaffee und Rotwein) oder an Anthocyanosiden (z. B. in Heidelbeeren) sind, reguliert werden. Ginkgo biloba schützt die Mitochondrien des Sehnervs vor oxidativem Stress. Experimentell kann die glaukomatöse Optikusneuropathie (GON) durch Hemmung der Aktivierung der Astrozyten verhindert werden. Diese können einerseits mechanisch aktiviert werden und durch die Blockade der epidermalen Wachstumsfaktorrezeptoren gehemmt werden. Anderseits können die Astrozyten biochemisch durch gesteigerte Endothelinproduktion mobilisiert werden und entsprechend mit sog. Endothelinblockern aufgehalten werden. Auch Stickstoffmonoxid-Synthase-2-(NOS-2-)Hemmer verhindern die Glaukomentwicklung. Die Hemmung der Matrix-Metalloproteinase-9 (MMP-9) beugt der Apoptose retinaler Ganglienzellen und der Gewebeumbildung vor.

Abstract

It is well established that an IOP reduction improves, on average, the prognosis of all types of glaucoma. It is also known, however, that even an ideal IOP does not stop progression in all patients. The insight into the pathogenesis of glaucomatous damage leads to new therapeutic approaches. Whilst most of these new avenues of treatment are still in the experimental phase, others, such as magnesium, Ginkgo, salt and fludrocortisone are already used by some physicians. Blood pressure dips can be avoided by intake of salt or fludrocortisone. Vascular regulation can be improved either locally by carbonic anhydrase inhibitors or systemically with magnesium or with low doses of calcium channel blockers. A number of other food ingredients such as polyphenolic flavonoids occurring in tea, coffee, dark chocolate or red wine and anthocyanosides found in bilberries have potential antioxidative effects. The oxidative stress at the level of the mitochondria can be reduced by Ginkgo biloba. Experimentally, glaucomatous optic neuropathy can be prevented by inhibition of astrocyte activation, either by blockage of epidermal growth factor receptor or by counteracting endothelin. Glaucomatous optic neuropathy can also be prevented by nitric oxide-2 synthase inhibition. Inhibition of matrix metalloproteinase-9 inhibits apoptosis of retinal ganglion cells and tissue remodelling. Up-regulation of heat shock proteins protects the retinal ganglion cells and the optic nerve head.

Schlüsselwörter

Glaukom - Pharmakologie - Biochemie

Key words

glaucoma - pharmacology - biochemistry
 

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