Nichtmedikamentöse interventionelle Perspektiven bei der AMD

Zusammenfassung

Die chirurgische Behandlung der AMD durch Zelltransplantation und Makularotation wurde bereits vor über 25 Jahren entwickelt. Aktuell wird die Injektionstherapie mit Inhibitoren von Wachstumsfaktoren erfolgreich angewendet. Dabei kann in etwa 30 % der Fälle eine Visusverbesserung erreicht werden. Grundsätzlich gelten für eine erfolgreiche Therapie mit Wachstumsfaktorinhibitoren als Voraussetzung: 1. Die RPE-Zellen müssen vorhanden und funktionstüchtig sein. 2. Die Photorezeptorzellen dürfen nicht degeneriert sein. Nach dieser Hypothese kann eine antivaskuläre Injektionstherapie anderenfalls nicht funktionieren und eine chirurgische Intervention ist dann indiziert. Da die chirurgische Entfernung von RPE-Zellen und Gefäßmembranen bei der AMD zu einer Zerstörung von Teilen der Basalmembran sowie der Bruch’schen Membran führt, erscheint eine Rekonstruktion dieser Schichten für eine erfolgreiche Therapie von entscheidender Bedeutung zu sein. Nach aktueller Studienlage zeigt die Makularotation die besten Langzeitergebnisse und stellt damit das chirurgische Verfahren der Wahl dar. Die Transplantation von RPE- oder IPE-Zellen bei AMD-Patienten hat demgegenüber bislang nicht zu einer signifikanten Visusverbesserung geführt. Unter den vielen möglichen Verfahren zur Rekonstruktion der zerstörten Basalmembran und der Bruch’schen Membran erscheint zukünftig die Verwendung eines Monolayers von Pigmentepithelzellen auf einem biologisch abbaubaren Substrat als das Erfolg versprechendste Verfahren. Außerdem können die transplantierten Zellen innerhalb des Monolayers genetisch gezielt modifiziert werden, um eine Rekonstruktion des Netzhaut-Aderhautkomplexes mittels Wachstumsfaktoren oder Inhibitoren von Neovaskularisationen zu unterstützen.

Abstract

Transplantation and translocation surgery for the treatment of AMD has been evaluated for over 25 years. More recently injections of inhibitors of vascularisation have been used with some success. Inhibitors of neovascularisation result in the recovery of vision in about 30 % of patients; however, we do not understand what criteria can be used to select patients who will respond to or will not respond to treatment with antivascularisation treatment. We have to assume that successful antivascularisation treatment will require first that the retinal pigment epithelial cells be present and functional and second that the photoreceptor cells should not be degenerated. We then hypothesise that if either of these two parameters are not present, antivascular treatment will not result in vision recovery and we must then consider surgical intervention. Surgical intervention for macular degeneration encompasses procedures from simple membrane extraction to macular rotation to cell transplantation or a combination of these procedures, however these procedures must take into account that vision recovery cannot be achieved without reconstruction of the retina-choroid complex. Since in AMD degeneration of the retinal pigment epithelial cells and vascular membranes removal results in damage to the basal lamina and possibly deeper layers of Bruch’s membrane, it will be necessary to reconstruct these damaged structures. In fact, transplantation of RPE cells or IPE cells has not resulted in any significant improvement in vision in AMD patients. Long-term follow-up of AMD patients following macular rotation surgery has shown that significant visual recovery is not maintained in most patients. Of the many approaches that could be used to reconstruct the damaged basal lamina and Bruch’s membrane the most promising would be the introduction of a monolayer of pigment cells on a “natural” biodegradable substratum. A natural substratum consisting of extracellular matrix proteins would allow the pigment cells to retain their differentiated characteristics and functions, including the degradation the substratum and production of the normal components of the basal lamina and Bruch’s membrane. In addition, the cells introduced as a monolayer can be engineered to carry specific genes to aid in the restructuring of the retina-choroid complex, such as growth factors and inhibitors of vascularisation.

Schlüsselwörter

Retina - Chorioidea - Glaskörper

Key words

retina - choroid - vitreous

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