Erhöhter Augeninnendruck für 7 Wochen induziert lokale Gefäßveränderungen im experimentellen Glaukommodell in vivo

Zusammenfassung

Hintergrund Peripapilläre Blutungen sind diagnostisch wegweisend für das Vorliegen des Glaukoms. Dennoch ist die Rolle der Gefäße der Retina und des Sehnervs in der Pathogenese des Glaukoms weitestgehend ungeklärt. Ziel dieser Studie war es, im experimentellen Glaukommodell die lokalen Veränderungen dieser Gefäße auf erhöhten Druck in vivo zu untersuchen.

Material und Methoden Das Glaukom wurde durch Veröden dreier episkleraler Venen des linken Auges von weiblichen Sprague-Dawley-Ratten induziert (n = 6). In vivo erfolgte eine Messung der Gefäßkaliber mittels peripapillärem Scan des SD-OCT (Heidelberg Engineering) als Baseline sowie 7 Wochen nach Augeninnendruckerhöhung. Die Tiere wurden anschließend euthanasiert, Querschnitte des Sehnervs wurden zur Anfärbung der Kapillaren mit Paraphenylendiamin angefertigt. Die kontralateralen Augen dienten als Kontrolle. Die Gefäßkaliber wurden fotografiert und verglichen.

Ergebnisse Der Augeninnendruck zeigte sich signifikant erhöht (p < 0,001). In Querschnitten des Sehnervs zeigte sich die Anzahl der Gefäße nicht signifikant verändert nach erhöhtem Augeninnendruck. Die Kaliber der Gefäße jedoch zeigten 7 Wochen nach Augeninnendruckerhöhung eine signifikante Reduktion (p < 0,001). Das Kaliber der großen retinalen Gefäße war ebenfalls deutlich reduziert um 9,22% (p < 0,05). Die Ergebnisse beziehen sich immer auf das Kontrollauge ohne erhöhten Augeninnendruck.

Schlussfolgerung Die Gefäße der Retina und die Kapillaren des Sehnervs reagieren sensitiv auf erhöhten Druck. Die Antwort der Gefäße kann zeigen, dass vaskuläre Veränderungen im Rahmen der Glaukomerkrankung entstehen und eröffnet somit weitere mögliche Therapieoptionen.

Abstract

Introduction Glaucoma is characterised by progressive loss of retinal ganglion cells and axons. Experimental research has concentrated on understanding the pathophysiological mechanisms involved in glaucomatous damage. It is still a matter of debate whether neurons or capillaries are primarily damaged by elevated intraocular pressure (IOP). The aim of this study was to detect IOP-induced vascular changes in the vessels of the optic nerve head and the main vessels of the retina in vivo.

Methods Experimental glaucoma was induced in adult Sprague Dawley rats by cauterisation of three episcleral veins of the left eye (n = 3). In vivo, retinal vessel calibre was measured manually using a peripapillary scan with SD-OCT (Heidelberg Engineering) at baseline and after seven weeks of IOP elevation. The animals were then sacrificed and the optic nerve was fixed with 30% glutaraldehyde and cross-sections stained with paraphenylene diamine to mark the vessels. Contralateral eyes served as controls. Pictures were taken and number of vessels, vessel calibre and area were calculated and compared.

Results IOP was significantly elevated (p < 0.001). In optic nerve cross sections, the number of capillaries did not differ significantly between animals with elevated IOP and controls. However, vessel calibre and area were significantly reduced (p < 0.001) in glaucomatous optic nerves. The calibre of the retinal vessels was significantly lowered – by 9.22% (p = 0.021).

Conclusion Retinal arterioles and optic nerve capillaries respond sensitively to abnormal pressure elevation in vivo, showing high and early vulnerability. The vascular responses may influence secondary neuronal responses, which culminate in the death of ganglion cells and blindness, as occurs in clinical glaucoma.

Schlüsselwörter

Glaukom - Kapillaren - erhöhter Augeninnendruck

Key words

experimental glaucoma - capillaries - high IOP

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