Ganglberger Matthias, Koschak Alexandra
Pharmacology and Toxicology, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria.
Channels (Austin). 2025 Dec;19(1):2480089. doi: 10.1080/19336950.2025.2480089. Epub 2025 Mar 25.
The visual process begins with photon detection in photoreceptor outer segments within the retina, which processes light signals before transmission to the thalamus and visual cortex. Cav1.4 L-type calcium channels play a crucial role in this process, and dysfunction of these channels due to pathogenic variants in corresponding genes leads to specific manifestations in visual impairments. This review explores the journey from basic research on Cav1.4 L-type calcium channel complexes in retinal physiology and pathophysiology to their potential as gene therapy targets. Moreover, we provide a concise overview of key findings from studies using different animal models to investigate retinal diseases. It will critically examine the constraints these models present when attempting to elucidate retinal channelopathies. Additionally, the paper will explore potential strategies for addressing Cav1.4 channel dysfunction and discuss the current challenges facing gene therapy approaches in this area of research.
视觉过程始于视网膜内光感受器外段的光子检测，在光信号传输到丘脑和视觉皮层之前，视网膜会对其进行处理。Cav1.4 L型钙通道在这一过程中起着至关重要的作用，相应基因的致病变异导致这些通道功能障碍，进而在视觉障碍中产生特定表现。本综述探讨了从视网膜生理学和病理生理学中Cav1.4 L型钙通道复合物的基础研究到其作为基因治疗靶点的潜力的历程。此外，我们简要概述了使用不同动物模型研究视网膜疾病的关键发现。它将批判性地审视这些模型在试图阐明视网膜通道病时所存在的局限性。此外，本文还将探讨解决Cav1.4通道功能障碍的潜在策略，并讨论该研究领域中基因治疗方法目前面临的挑战。
