ArticleHuman molecular genetics2022
Multiomics analyses reveal early metabolic imbalance and mitochondrial stress in neonatal photoreceptors leading to cell death in Pde6brd1/rd1 mouse model of retinal degeneration.
Article in Human molecular genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 61 citations in OpenAlex.
- Rod photoreceptors have a dual dependency on both aerobic glycolysis and OXPHOS and diverge metabolically from other retinal neurons.Science advances · 2026Article
- Revisiting retinal and macular degeneration in the genomics era.Nature reviews. Genetics · 2026Review
- Redox imbalance dictates dependence on GOT1 versus GOT2 for rod photoreceptor health during aging and stress.Redox biology · 2026Article
- Quantitative Flavoprotein Fluorescence Parameters in Retinal and Optic Nerve Diseases: A Scoping Review.Journal of clinical medicine · 2026Review
- Halofantrine protects photoreceptors in multiple models of retinal degeneration.Research square · 2026Article
- In vivo elastography of the human retina using light-evoked intrinsic actuation.bioRxiv : the preprint server for biology · 2026Article
- Redox imbalance dictates dependence on GOT1 versus GOT2 for rod photoreceptor health during aging and stress.bioRxiv : the preprint server for biology · 2026Article
- Dysfunction of α2δ4 leads to photoreceptor degeneration through disrupted synaptic mitochondria and calcium crosstalk.Cell death & disease · 2026Article
- Interpretable Aging Signatures in Human Retinal Cell Types Revealed by Single-Cell RNA Sequencing and Sparse Logistic Regression.Ophthalmology science · 2026Article
- Elucidating the genetic landscape of inherited retinal disorders in India.Human genomics · 2026Review
- Modulation of Aerobic Glycolysis Genes During the Progression of Retinitis Pigmentosa.Investigative ophthalmology & visual science · 2026Article
- Single-Cell Transcriptomics onBiomedicines · 2025Article
- Reactive Oxygen Species Regulation Across Retinitis Pigmentosa Animal Models: A 25-Year Systematized Review.Molecular neurobiology · 2025Review
- Comparative transcriptomic analysis of retinal response to diverse cellular stresses reveals relative contributions of different cell death processes and signalling networks.Cell death & disease · 2025Article
- Article
- Quantitative proteomic profiling reveals sexual dimorphism in the retina and RPE of C57BL6 mice.Biology of sex differences · 2024Article
- Epigenome-metabolism nexus in the retina: implications for aging and disease.Trends in genetics : TIG · 2024Review
- Pathways controlling neurotoxicity and proteostasis in mitochondrial complex I deficiency.Human molecular genetics · 2024Article
- Gene Therapies for Retinitis Pigmentosa that Target Glucose Metabolism.Cold Spring Harbor perspectives in medicine · 2024Review
- Acetazolamide Challenge Changes Outer Retina Bioenergy-Linked and Anatomical OCT Biomarkers Depending on Mouse Strain.Investigative ophthalmology & visual science · 2024Article
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Authors and funding
14 authors at 5 institutions in 4 countries.
Funding
Abstract
Retinal diseases exhibit extensive genetic heterogeneity and complex etiology with varying onset and severity. Mutations in over 200 genes can lead to photoreceptor dysfunction and/or cell death in retinal neurodegeneration. To deduce molecular pathways that initiate and/or drive cell death, we adopted a temporal multiomics approach and examined molecular and cellular events in newborn and developing photoreceptors before the onset of degeneration in a widely-used Pde6brd1/rd1 (rd1) mouse, a model of autosomal recessive retinitis pigmentosa caused by PDE6B mutations. Transcriptome profiling of neonatal and developing rods from the rd1 retina revealed early downregulation of genes associated with anabolic pathways and energy metabolism. Quantitative proteomics of rd1 retina showed early changes in calcium signaling and oxidative phosphorylation, with specific partial bypass of complex I electron transfer, which precede the onset of cell death. Concurrently, we detected alterations in central carbon metabolism, including dysregulation of components associated with glycolysis, pentose phosphate and purine biosynthesis. Ex vivo assays of oxygen consumption and transmission electron microscopy validated early and progressive mitochondrial stress and abnormalities in mitochondrial structure and function of rd1 rods. These data uncover mitochondrial overactivation and related metabolic alterations as determinants of early pathology and implicate aberrant calcium signaling as an initiator of higher mitochondrial stress. Our studies thus provide a mechanistic framework with mitochondrial damage and metabolic disruptions as early drivers of photoreceptor cell death in retinal degeneration.
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