Metabolic transcriptomics dictate responses of cone photoreceptors to retinitis pigmentosa.

ABSTRACT: 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 l

SUBMITTER: Lee SJ 

PROVIDER: S-EPMC10591869 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature