Institute for Ophthalmic Research, University of Tübingen, Elfriede-Aulhorn-Strasse 5-7, 72076 Tübingen, Germany.
Biolog Life Science Institute, 28199 Bremen, Germany.
Genes (Basel). 2019 Jun 14;10(6):453. doi: 10.3390/genes10060453.
Photoreceptor physiology and pathophysiology is intricately linked to guanosine-3',5'-cyclic monophosphate (cGMP)-signaling. Here, we discuss the importance of cGMP-signaling for the pathogenesis of hereditary retinal degeneration. Excessive accumulation of cGMP in photoreceptors is a common denominator in cell death caused by a variety of different gene mutations. The cGMP-dependent cell death pathway may be targeted for the treatment of inherited photoreceptor degeneration, using specifically designed and formulated inhibitory cGMP analogues. Moreover, cGMP-signaling and its down-stream targets may be exploited for the development of novel biomarkers that could facilitate monitoring of disease progression and reveal the response to treatment in future clinical trials. We then briefly present the importance of appropriate formulations for delivery to the retina, both for drug and biomarker applications. Finally, the review touches on important aspects of future clinical translation, highlighting the need for interdisciplinary cooperation of researchers from a diverse range of fields.
光感受器的生理学和病理生理学与鸟苷酸-3',5'-环单磷酸（cGMP）信号密切相关。在这里，我们讨论了 cGMP 信号对遗传性视网膜变性发病机制的重要性。cGMP 在光感受器中的过度积累是由各种不同基因突变引起的细胞死亡的共同特征。cGMP 依赖性细胞死亡途径可能成为治疗遗传性光感受器变性的靶点，使用专门设计和配制的抑制 cGMP 类似物。此外，cGMP 信号及其下游靶标可用于开发新的生物标志物，有助于监测疾病进展并揭示未来临床试验中的治疗反应。然后，我们简要介绍了适当制剂对视网膜给药的重要性，包括药物和生物标志物应用。最后，该综述涉及未来临床转化的重要方面，强调了来自不同领域的研究人员跨学科合作的必要性。
