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CC BY-NC-ND 1.0 · Klin Monbl Augenheilkd 2017; 234(03): 335-342
DOI: 10.1055/s-0043-101820
Übersicht
Georg Thieme Verlag KG Stuttgart · New York

Optogenetik – eine Chance für fortgeschrittene retinale Dystrophien

Optogenetics: A Therapeutic Option for Advanced Retinal Dystrophies
A. Swiersy
DFG-Forschungszentrum für Regenerative Therapien Dresden (CRTD), Technische Universität Dresden
,
S. D. Klapper
DFG-Forschungszentrum für Regenerative Therapien Dresden (CRTD), Technische Universität Dresden
,
V. Busskamp
DFG-Forschungszentrum für Regenerative Therapien Dresden (CRTD), Technische Universität Dresden
› Author Affiliations
Further Information

Publication History

eingereicht 09 November 2016

akzeptiert 11 January 2017

Publication Date:
02 March 2017 (online)

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Zusammenfassung

Die Optogenetik nutzt genetisch modifizierte lichtaktive Proteine, um Zellen durch Licht nicht invasiv zu manipulieren. Der Prototyp dieser Proteine ist Channelrhodopsin2 (ChR2), ein unselektiver Kationenkanal. Dieser kann elektrisch erregbare Zellen durch Lichtimpulse depolarisieren. Die Kombination von Channelrhodopsin und Halorhodopsin (eNpHR), eine hyperpolarisierende lichtgetriebene Cl−-Pumpe, ermöglicht eine komplexe Modulation neuronaler Aktivität sowohl in vitro als auch in vivo. Sehr schnell stellte sich heraus, dass die Optogenetik für die Behandlung von Sehbehinderungen, die mit der Degeneration der Photorezeptoren einhergehen, gute Chancen zur Therapie bietet. Dabei werden funktionslose Photorezeptoren durch die ektopische Expression der hyperpolarisierenden Pumpe eNpHR reaktiviert. Aber auch andere Zellen der Retina können durch die induzierte Expression von ChR2 die Aufgabe des Lichtempfangs übernehmen und damit zu künstlichen Photorezeptoren werden. Mit diesem Übersichtsartikel möchten wir eine kurze Einführung zur Retina und deren Rolle sowohl in der physiologischen als auch in der pathologischen Lichtwahrnehmung geben. Weiterhin werden optogenetische Strategien zur Wiederherstellung der Lichtwahrnehmungen aufgezeigt und strukturelle sowie funktionelle Eigenschaften der auf Rhodopsin basierenden optogenetischen Werkzeuge diskutiert. Letztendlich wird die Anwendbarkeit für die Wiederherstellung des Sehvermögens durch die Optogenetik bewertet.

Abstract

Optogenetics refers to the genetic modification of cells to express light-sensitive proteins, which mediate ion flow or secondary signalling cascades upon light exposure. Channelrhodopsin, the most famous example, is an unselective cation channel, which opens when exposed to blue light, thus mediating the depolarisation of the expressing cell. Along with other light-sensitive proteins such as the chloride pump eNpHR, which mediates light-activated hyperpolarisation, the optogenetic toolset offers a wide range of non-invasive single cell manipulations. Due to the direct modulation of the membrane potential, the in-vivo and in-vitro application of optogenetics in neuronal cells seemed to be of outstanding interest. Soon it became evident that these tools are well-suited to treat retinas of patients suffering from photoreceptor degeneration, independently of the underlying mutation. The ectopic expression of channelrhodopsin or eNpHR may cause inactive photoreceptors or other, intact cells of the retina to become sensitive to light. Thus, the most basic function of the retina, the perception of light, can be restored. This review gives a short overview of the retinal structure as well as its physiological and pathological function as the primary light-perceiving tissue. We will focus on different optogenetic strategies to restore visual function in previously blind retinas.

Schlüsselwörter

Genetik - Retina - Optogenetik - Channelrhodopsin - retinale Dystrophien

Key words

genetics - retina - optogenetics - channelrhodopsin - retinal dystrophies
 

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