大多数色素性视网膜炎（RP）的突变起因于杆状光感受器，但随后受累的圆锥光感受器负责高分辨率的日光和彩色视觉，导致该疾病的最严重特征。我们使用质谱法跟踪向外视网膜传递的13C代谢产物，并使用单细胞RNA测序评估光感受器转录组。S锥代谢转录组表明参与三羧酸循环且对氧化磷酸化的ROS特征产生持续反应，我们将其与其组蛋白修饰转录组联系起来。肿瘤坏死因子（TNF）及其下游效应物RIP3通过线粒体功能障碍诱导和激活ROS的产生，在RP中，S锥在早期细胞凋亡过程中发生。长/中波长（L/M）锥体转录组显示增强的糖酵解能力，这维持了它们在RP进展过程中的功能。随着细胞外葡萄糖的逐渐减少，L/M锥体通过乳酸代谢得以长期休眠。版权所有© 2023 The Author(s). 由Elsevier Inc.出版。保留所有权利。

Most mutations in retinitis pigmentosa (RP) arise in rod photoreceptors, but cone photoreceptors, responsible for high-resolution daylight and color vision, are subsequently affected, causing the most debilitating features of the disease. We used mass spectroscopy to follow 13C metabolites delivered to the outer retina and single-cell RNA sequencing to assess photoreceptor transcriptomes. The S cone metabolic transcriptome suggests engagement of the TCA cycle and ongoing response to ROS characteristic of oxidative phosphorylation, which we link to their histone modification transcriptome. Tumor necrosis factor (TNF) and its downstream effector RIP3, which drive ROS generation via mitochondrial dysfunction, are induced and activated as S cones undergo early apoptosis in RP. The long/medium-wavelength (L/M) cone transcriptome shows enhanced glycolytic capacity, which maintains their function as RP progresses. Then, as extracellular glucose eventually diminishes, L/M cones are sustained in long-term dormancy by lactate metabolism.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.