Über die Klärung pathopysiologischer Ursachen genetisch bedingter Erkrankungen

Zusammenfassung

Evidenzbasierte Augenheilkunde fußt auf der Kenntnis pathophysiologischer Mechanismen auf molekularer Ebene. Ein Beispiel hierfür ist die anti-VEGF-Therapie zur Behandlung der feuchten Form der altersabhängigen Makuladegeneration. Ihr therapeutischer Erfolg basiert auf der Neutralisation einer Sorte von Molekül, dem VEGF-A. Die Untersuchung der Ursachenkette genetisch bedingter Erkrankungen bietet die besondere Gelegenheit, Krankheitsprozesse auf molekularer Ebene zu klären und molekular genaue Therapien zu entwickeln. Vom identifizierten Gen erfolgt die Analyse des Genprodukts und seiner Mutanten-Formen, wobei Tiermodelle als auch isolierte Moleküle im Expressionssystem untersucht werden. Somit kommt der Untersuchung der Pathomechanismen eine besondere Rolle zu. Mit diesem Artikel soll eine Orientierung über dieses Gebiet gegeben werden, über seine Methoden und grundlegende Pathomechanismen. Des Weiteren soll anhand von Beispielen gezeigt werden, wie die Analyse der Pathomechanismen genetisch bedingter Erkrankungen zum Verständnis erworbener Erkrankungen und zu neuen Therapieansätzen geführt hat.

Abstract

Evidence-based ophthalmology relies on a knowledge of the pathophysiological mechanisms at the molecular level. An example is the anti-VEGF therapy to treat the wet form of age-related macular degeneration. Its therapeutic effect is due to the neutralisation of a single type of molecule, the VEGF-A. The analysis of pathophysiological mechanisms of inherited diseases represents a unique opportunity to develop precise molecular therapeutic approaches. This analysis begins with the identification of the responsible gene which is followed by investigation of the function of its gene product along with the mutation-dependent changes using animal models and investigation of single molecules in expression systems. In this process the investigation of the pathomechanisms plays a central role. This review provides an orientation about studies on the pathophysiology of inherited diseases with a description of its methods and basic pathomechanisms. Furthermore, examples will be given on how the analysis of inherited retinal diseases has led to an understanding of the pathomechanisms of acquired diseases such as age-dependent macular degeneration and to the development of new therapeutic approaches.

Schlüsselwörter

Retina - Pathologie - Genetik - Protein-Sortierung - Pathophysiologie - Tiermodelle

Key words

genetics - Pathology - Retina - trafficking - pathopyhsiology - animal models

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