Méjécase Cécile, Nair Neelima, Sarkar Hajrah, Soro-Barrio Pablo, Toms Maria, Halliday Sophia, Linkens Katy, Jaroszynska Natalia, Maurer Constance, Owen Nicholas, Moosajee Mariya
Development, Ageing and Disease, UCL Institute of Ophthalmology, London EC1V 9EL, UK.
Ocular Genomics and Therapeutics, The Francis Crick Institute, London NW1 1AT, UK.
Antioxidants (Basel). 2024 Dec 23;13(12):1587. doi: 10.3390/antiox13121587.
Reactive oxygen species (ROS) within the retina play a key role in maintaining function and cell survival. However, excessive ROS can lead to oxidative stress, inducing dysregulation of metabolic and inflammatory pathways. The zebrafish models choroideremia (CHM), an X-linked chorioretinal dystrophy, which predominantly affects the photoreceptors, retinal pigment epithelium (RPE), and choroid. In this study, we examined the transcriptomic signature of the zebrafish retina to reveal the upregulation of cytokine pathways and glia migration, upregulation of oxidative, ER stress and apoptosis markers, and the dysregulation of glucose metabolism with the downregulation of glycolysis and the upregulation of the oxidative phase of the pentose phosphate pathway. Glucose uptake was impaired in the retina using the 2-NBDG glucose uptake assay. Following the overexpression of human , partial rescue was seen with the preservation of photoreceptors and RPE and increased glucose uptake, but without modifying glycolysis and oxidative stress markers. Therapies targeting glucose metabolism in CHM may represent a potential remedial approach.
视网膜内的活性氧（ROS）在维持功能和细胞存活中起关键作用。然而，过量的ROS会导致氧化应激，引发代谢和炎症途径的失调。斑马鱼模型表现出脉络膜视网膜病变（CHM），这是一种X连锁的脉络膜视网膜营养不良，主要影响光感受器、视网膜色素上皮（RPE）和脉络膜。在本研究中，我们检测了斑马鱼视网膜的转录组特征，以揭示细胞因子途径和神经胶质迁移的上调、氧化、内质网应激和凋亡标志物的上调，以及葡萄糖代谢的失调，其中糖酵解下调，磷酸戊糖途径氧化阶段上调。使用2-NBDG葡萄糖摄取试验发现视网膜中的葡萄糖摄取受损。在过表达人[此处原文缺失相关内容]后，观察到部分挽救，光感受器和RPE得以保留，葡萄糖摄取增加，但糖酵解和氧化应激标志物未改变。针对CHM中葡萄糖代谢的治疗可能代表一种潜在的补救方法。
