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Mögliche Rolle von Alkylphosphocholinen bei der Ablatio-Chirurgie

Possible role of alkylphosphocholines in retinal reattachment surgery

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Zusammenfassung

Hintergrund

Die proliferative Vitreoretinopathie (PVR) gilt als eine der schwersten Komplikationen nach Ablatio-Chirurgie. Bisher konnte sich keine Pharmakotherapie zur Kontrolle der zellbiologischen Komponente dieser Erkrankung klinisch etablieren. Ziel unserer Studie war es, den Einfluss von Alkylphosphocholinen (APCs; hier: Erucylphosphocholin; ErPC), neuen pharmakologischen Substanzen mit antiproliferativen Eigenschaften, auf die intraretinale Proliferation nach experimentell induzierter Netzhautablösung an einem etablierten in vivo Modell zu untersuchen.

Methoden

Am Kaninchenauge wurde eine Netzhautablösung durch subretinale Injektion mit einer Mikropipette induziert. An Tag 1 oder an Tag 2 erfolgte die intravitreale Injektion von Erucylphosphocholin (ErPC). Bromodeoxyuridine (5-bromo-2-deoxyuridine, BrdU) wurde an Tag 3 injiziert. Nach Fixierung des Gewebes erfolgte eine Dreifachmarkierung der Netzhaut mit Anti-BrdU (Proliferationsmarker), Isolectin B4 (Marker für retinale Mikrogliazellen) und Anti-Vimentin (Marker für retinale Müller-Gliazellen). Die Anzahl proliferierender, also Anti-BrdU-markierter Zellen pro mm Netzhaut wurde am konfokalen Laser-Scanning-Mikroskop bestimmt. Die Toxizität wurde anhand von gefärbten Gewebeschnitten am Lichtmikroskop sowie ultrastrukturell am Elektronenmikroskop beurteilt.

Ergebnisse

Nach einmaliger intravitrealer Gabe von Erucylphosphocholin (ErPC) zeigte sich eine signifikante Abnahme der Proliferation nichtneuraler retinaler Zellen an Tag 3 nach Induktion einer Netzhautablösung am Kaninchenauge. Eine Injektion an Tag 1 war der Injektion an Tag 2 nach Netzhautablösung überlegen. Für keine der applizierten ErPC-Konzentrationen war morphologisch eine retinale Toxizität nachweisbar.

Schlussfolgerungen

Alkylphosphocholine sind neue Substanzen, die eine Inhibition der intraretinalen Proliferation nach Netzhautablösung im Tiermodell bewirken. Möglicherweise könnten APCs zukünftig zur Prophylaxe einer PVR bei der Ablatio-Chirurgie in noch zu definierenden Situationen intravitreal gegeben werden, um die zellbiologische Komponente der Erkrankung zu kontrollieren. Unabdingbare Voraussetzung dafür sind jedoch weitere, langfristige Untersuchungen zur Toxizität dieser neuen Substanzgruppe.

Abstract

Background

Proliferative vitreoretinopathy (PVR) is a major complication after retinal detachment surgery, but there is no established pharmacotherapy available to control the cell biology of the disease. The aim of this study was to investigate the role of alkylphosphocholines [APCs; erucylphosphocholine (ErPC) was used in this study], novel pharmacologic substances with antiproliferative properties, on intraretinal proliferation initiated by experimental retinal detachment in a well-established in vivo model.

Methods

Retinal detachments were created in adult pigmented rabbits. ErPC was injected intravitreally on either day 1 or day 2 after detachment. Bromodeoxyuridine (5-bromo-2-deoxyuridine, BrdU) was injected on day 3. Following fixation, retinas were triple-labelled with anti-BrdU (proliferation marker), Isolectin B4 (retinal microglia marker), and anti-vimentin (retinal Mueller glia cell marker). The number of anti-BrdU-labelled cells per millimeter of retina was determined from sections imaged by laser scanning confocal microscopy. Toxicity was assessed by light and electron microscopy.

Results

A single intravitreal injection of ErPC had a significant effect on reducing the number of proliferating non-neural retinal cells on day 3 after experimental retinal detachment in the rabbit. Injection of ErPC on day 1 was more effective than when given on day 2. No evidence of toxicity was observed in the retina on day 3 for any of the conditions.

Conclusions

APCs are novel pharmacologic substances that significantly inhibited intraretinal proliferation after experimental retinal detachment in this in vivo model. They could be considered as an adjunct therapy at the time of retinal reattachment surgery to potentially prevent proliferative vitreoretinal diseases such as PVR. However, long-term toxicity studies must be performed before APCs can be considered for clinical application.

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Authors and Affiliations

  1. Augenklinik der Ludwig-Maximilians-Universität, Mathildenstraße 8, 80336, München, Deutschland

    K.H. Eibl, A. Gandorfer & A. Kampik

  2. Neuroscience Research Institute, University of California, Santa Barbara, CA, USA

    G.P. Lewis, K. Betts, K.A. Linberg & S.K. Fisher

  3. Department of Cellular Molecular and Developmental Biology, University of California, SantaBarbara, CA, USA

    S.K. Fisher

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  1. K.H. Eibl
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  2. G.P. Lewis
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  3. K. Betts
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  4. K.A. Linberg
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  5. A. Gandorfer
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  6. S.K. Fisher
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  7. A. Kampik
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Correspondence to K.H. Eibl.

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Eibl, K., Lewis, G., Betts, K. et al. Mögliche Rolle von Alkylphosphocholinen bei der Ablatio-Chirurgie. Ophthalmologe 104, 972–977 (2007). https://doi.org/10.1007/s00347-007-1574-1

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