Bedeutung von transienten Rezeptorpotenzialkanälen für die okuläre Oberfläche: Einblick und Ausblick – von der Laborforschung zur klinischen Praxis

Zusammenfassung

Für eine optimale visuelle Funktion ist eine Augenoberfläche mit einem vitalen Epithelverband und stabilen Tränenfilm erforderlich. Eine Vielzahl von endogenen und externen Faktoren kann die empfindliche Homöostase der Augenoberfläche beeinflussen und zu einem „trockenen Auge“ führen. Studien im letzten Jahrzehnt haben gezeigt, dass Ca²⁺ ein wichtiger Faktor bei der Kontrolle der Epithelfunktion der Augenoberfläche ist. Dabei konnten insbesondere transiente Rezeptorpotenzialkanäle (TRPs) als wichtige Komponenten in Hornhaut- und Bindehautzellen identifiziert werden. Die TRPs sind nicht selektive Kationenkanäle, die als molekulare Sensoren wärme-, nozi- bzw. osmosensibel sind. Unsere Ca²⁺-Imaging- und Patch-Clamp-Studien zeigen, dass die Aktivität von 2 TRP-Isoformen, TRPV1 und TRPM8, durch Änderungen der Osmolarität, der Außentemperatur und einiger endogener Substrate moduliert werden kann. Diese TRPs werden sowohl an nicht neuronalen als auch an neuronalen Hornhautzellen exprimiert. Darüber hinaus beeinflussen diese Wechselwirkungen die Expression von Zytokinen, die inflammatorische Prozesse fördern oder hemmen und damit einen wichtigen Beitrag zur Physiologie des Trockenen Auges leisten. Zusammengenommen führen diese Ergebnisse nicht nur zu einem besseren Verständnis der Pathophysiologie von Schmerz- und Entzündungsreaktionen der Augenoberfläche. Diese Studien können auch neue Wege aufzeigen, um die Pathophysiologie der Krankheit zu verstehen und die Entwicklung neuer therapeutischer Angriffspunkte beim Syndrom des Trockenen Auges fördern.

Abstract

Optimal vision requires an ocular surface with vital epithelial coverage and a stable tear film. A multitude of endogenous and external factors may alter this delicate balance. Studies over the last decade have established that Ca²⁺ is an important factor in the control of ocular surface epithelial function and has led to the identification of critical components. In particular, transient receptor potential channels (TRPs) have been identified as important components in corneal and conjunctival cells. These channels encompass a group of ion channels of numerous cell types. TRPs are nonselective cation channels which are Ca²⁺ permeable. Most TRPs serve as thermosensitive molecular sensors (thermo-TRPs). Our Ca²⁺ imaging and patch-clamp studies indicate that the activity of two TRP isoforms, TRPV1 and TRPM8, can be modulated by changes in external temperature osmolarity and some endogenous substrates. These TRPs are expressed on both non-neuronal and neuronal corneal cells. Furthermore, these interactions affect control of cytokines either promoting or inhibiting inflammation, one of the key findings in dry eye syndrome. Taken together, these results not only lead to a better understanding of the pathophysiology in pain and inflammation reactions on the surface of the eye, but these studies may also offer new avenues to understand the pathophysiology of the disease and support the development of novel therapeutic targets in dry eye syndrome.

Schlüsselwörter

Hornhaut - Trockenes Auge - proinflammatorische Zytokine - TRP-Kanäle

Key words

cornea - dry eye - pro-inflammatory cytokines - TRP channels

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