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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Prof. Gabriele Thumann
IZKF Biomat, RWTH Aachen
Pauwelsstr. 30
52074 Aachen
Telefon: ++ 49/2 41/8 03 57 28
Fax: ++ 49/2 21/9 40 29 23
eMail: Gthumann@ukaachen.de
