Photorezeptortransplantation in die degenerative Netzhaut

 

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Zusammenfassung

Sehbeeinträchtigungen und Erblindung aufgrund des Verlusts von Photorezeptoren stellen einen der Hauptgründe für Behinderungen in industrialisierten Gesellschaften dar. Während Stäbchenphotorezeptoren Seheindrücke unter schwachen Lichtverhältnissen vermitteln, liefern Zapfenphotorezeptoren fokussierte visuelle Eindrücke bei Tageslicht und erlauben die Wahrnehmung von Farben. Verschiedene therapeutische Strategien, zu denen auch zellbasierte Interventionen zählen, werden derzeit zur Behandlung eines Sehverlusts entwickelt. Während der letzten Dekade konnten große Fortschritte im Ersatz von Photorezeptoren in vorklinischen Tiermodellen erzielt werden. Dies beinhaltete die Klärung notwendiger Voraussetzungen, wie dem optimalen ontogenetischen Stadium für transplantierbare Photorezeptoren, zellspezifische Anreicherungsmethoden und robuste Transplantationstechniken. Außerdem konnten erste Studien Hinweise auf funktionale Verbesserungen nach Photorezeptortransplantation in Mausmodelle mit retinaler Dysfunktion liefern. Des Weiteren erlauben bedeutende Fortschritte in der Zellkulturtechnik die Generierung von photorezeptorenthaltenden retinalen Organoiden, die aus pluripotenten Stammzellen gewonnen werden und eine theoretisch unbegrenzte Quelle zur Produktion von Photorezeptortransplantaten darstellen. Interessanterweise könnte der kürzlich beschriebene Transfer von zytoplasmatischem Material zwischen Spender- und Empfängerphotorezeptoren eine weitere Behandlungsoption für Ansätze zur Zelltransplantation darstellen. In dieser Übersicht fokussieren wir uns auf die wichtigsten Entwicklungen innerhalb des Feldes der Photorezeptortransplantation, wobei wir Fortschritte, Herausforderungen und Hürden zur Entwicklung von Photorezeptortransplantationen hin zu klinischen Anwendungen diskutieren.

Abstract

Vision impairment and blindness due to photoreceptor loss represents one of the major causes for disability in industrialized societies. Whereas rod photoreceptors allow vision under dim light conditions, cone photoreceptors provide high-acuity vision in daylight conditions and color detection. Several therapeutic strategies are currently developed to repair vision loss, including cell-based interventions. Within the last decade, major progress regarding the replacement of photoreceptors by transplantation has been made in pre-clinical animal models. This includes defining the necessary conditions, like the optimal ontogenetic stage of transplantable donor photoreceptors, cell-specific enrichment procedures and robust transplantation technologies. Moreover, first studies provided evidence for functional improvements by photoreceptor transplantation in mouse models of retinal dysfunction. Furthermore, advances in cell culture technology were made by introducing methods to generate photoreceptor-containing retinal organoids, derived from pluripotent stem cells, that provide theoretically unlimited sources for the production of photoreceptor transplants. Interestingly, the recently identified transfer of cytoplasmic material between donor and host photoreceptors might represent an additional treatment option for cell transplantation approaches. Within this review, we focus on the main developments within the photoreceptor transplantation field and discuss important achievements, challenges and hurdles to develop photoreceptor transplantation towards clinical applications.

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