Gentherapie bei Hornhauterkrankungen

Zusammenfassung

In der Vergangenheit wurden euphorische Erwartungen in die Gentherapie geweckt, die aber bisher nicht nur nicht erfüllt, sondern im Gegenteil wegen eines Ausbleibens konkreter klinischer Erfolge sowie des Eintretens tragischer Zwischenfälle enttäuscht wurden. Trotz des großen Zukunftspotenzials der Gentherapie werden wohl für längere Zeit zahlreiche gentherapeutische Pilotstudien abgebrochen werden. Aber trotz aller Misserfolge werden Krankheiten für experimentelle Protokolle, die beispielsweise nur eine vorübergehenden Genexpression vorsehen oder solche, die sich auf einzelne Organe beschränken und daher nur eine niedrige Dosis des Vehikels (Vektors) benötigen, weiterhin Ziel experimenteller Gentransferversuche bleiben. Wegen seiner guten und selektiven Erreichbarkeit, des geringen Volumens und des dadurch bedingten geringen Bedarfs an Genfähren sowie seines besonderen immunologischen Status ist gerade das Auge als potenzielles Zielorgan hervorragend geeignet. Die Hornhauttransplantation ist eine Indikation mit verbesserbarer Prognose, die vom Methodenkatalog der Gentransferprotokolle profitieren kann. Die Hornhaut steht zudem vor einer Transplantation einem Gentransfer ex vivo zur Verfügung. Die Augenheilkunde könnte daher beim klinischen Gentransfer eine Pionierstellung einnehmen. Eine Literatursynopse beschreibt den gegenwärtigen Stand der experimentellen Verbesserung der Hornhauttransplantation, der Beeinflussung der Narbenbildung, der Neovaskularisation und der Herpesinfektion der Kornea. Das wesentliche Problem der Gentherapie ist die nicht zufrieden stellende Technik des Gentransfers. Die Schwierigkeiten und die aktuellen Verbesserungen werden erörtert.

Abstract

Gene therapy raised euphoric expectations in the past that have yet to be met and have even been lowered due to the absence of concrete clinical successes and the occurrence of some tragic incidents. In spite of the great future potential of gene therapy, numerous pilot studies in this field will probably be discontinued for a long time. However, despite these failures, diseases will continue to be the aim of gene transfer studies with experimental protocols using only temporary gene expression or those restricted to individual organs and thus requiring only a low dose of the vehicle (vector). The eye is exceptionally well suited as a potential target organ because of its good and selective accessibility, low volume and the resultant low number of gene ferries required as well as its special immunological status. The prognosis of corneal grafting can be improved and profit from the methods catalogue of gene transfer protocols. Moreover, the cornea can be used for ex vivo gene transfer before grafting. Ophthalmology could thus occupy a pioneer position in clinical gene transfer. A survey of the literature describes the current state of experimental improvement in corneal grafting, the effect on scarring, neovascularization, and herpetic corneal infection. The essential problem of gene therapy is the unsatisfactory gene transfer technique. Difficulties and current improvements are discussed.

Schlüsselwörter

Gentransfer - Vektoren - Hornhauttransplantation - Narbenbildung - Neovaskularisation - Herpesinfektion

Key words

Gene transfer - vectors - corneal grafting - scarring - neovascularization - herpes infection

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