ArticleInvestigative ophthalmology & visual science2023
Dysregulated Arginine Metabolism Is Linked to Retinal Degeneration in Cep250 Knockout Mice.
Article in Investigative ophthalmology & visual science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 11 citations in OpenAlex.
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- Interleukin 27-induced photoreceptor survival is associated with suppression of a novel Muller glia subpopulation.Cell communication and signaling : CCS · 2026Article
- Loss of Kv8.2 in the Mouse Retina Is Associated With Altered One-Carbon Metabolism.Journal of neurochemistry · 2026Article
- Integrated omics reveal the effects of vitamin D deficiency on gut microbiota and plasma metabolism in experimental autoimmune uveitis.Journal of neuroinflammation · 2026Article
- Exploratory Metabolomic Fingerprinting of Aqueous Humor in Healthy Horses and Donkeys, and in Horses with Ocular Pathologies.Animals : an open access journal from MDPI · 2025Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: Degeneration of retinal photoreceptors is frequently observed in diverse ciliopathy disorders, and photoreceptor cilium gates the molecular trafficking between the inner and the outer segment (OS). This study aims to generate a homozygous global Cep250 knockout (KO) mouse and study the resulting phenotype. Methods: We used Cep250 KO mice and untargeted metabolomics to uncover potential mechanisms underlying retinal degeneration. Long-term follow-up studies using optical coherence tomography (OCT) and electroretinography (ERG) were performed. Results: OCT and ERG results demonstrated gradual thinning of the outer nuclear layer (ONL) and progressive attenuation of the scotopic ERG responses in Cep250-/- mice. More TUNEL signal was observed in the ONL of these mice. Immunostaining of selected OS proteins revealed mislocalization of these proteins in the ONL of Cep250-/- mice. Interestingly, untargeted metabolomics analysis revealed arginine-related metabolic pathways were altered and enriched in Cep250-/- mice. Mis-localization of a key protein in the arginine metabolism pathway, arginase 1 (ARG1), in the ONL of KO mice further supports this model. Moreover, adeno-associated virus (AAV)-based retinal knockdown of Arg1 led to similar architectural and functional alterations in wild-type retinas. Conclusions: Altogether, these results suggest that dysregulated arginine metabolism contributes to retinal degeneration in Cep250-/- mice. Our findings provide novel insights that increase understanding of retinal degeneration in ciliopathy disorders.
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