ArticleProceedings of the National Academy of Sciences of the United States of America2010
Inhibition of ceramide biosynthesis preserves photoreceptor structure and function in a mouse model of retinitis pigmentosa.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 117 citations in OpenAlex.
- Integrated Proteomic and Lipidomic Profiling of Aqueous Humor Reveals Inflammatory Signatures in Retinitis Pigmentosa.Biomedicines · 2026Article
- Single-Cell Transcriptomics in Inherited Retinal Dystrophies: Current Findings and Emerging Perspectives.Genes · 2025Review
- Nanotherapy for Neural Retinal Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Gene therapy for age-related macular degeneration: a promising frontier in vision preservation.Cell communication and signaling : CCS · 2025Review
- Elevated Very-Long-Chain Ceramides in the Vitreous Humor of Patients With Proliferative Diabetic Retinopathy.Investigative ophthalmology & visual science · 2025Article
- Inhibiting De Novo Biosynthesis of Ceramide by L-Cycloserine Can Prevent Light-Induced Retinal Degeneration in Albino BALB/c Mice.International journal of molecular sciences · 2024Article
- Macular telangiectasia type 2 in a patient with Down syndrome: A possible association.American journal of ophthalmology case reports · 2024Article
- Mutant mice with rod-specific VPS35 deletion exhibit retinal α-synuclein pathology-associated degeneration.Nature communications · 2024Article
- Recent Advances in Nanomedicine for Ocular Fundus Neovascularization Disease Management.Advanced healthcare materials · 2024Review
- Sphingolipid biosynthetic inhibitor L-Cycloserine prevents oxidative-stress-mediated death in an in vitro model of photoreceptor-derived 661W cells.Experimental eye research · 2024Article
- Untargeted and temporal analysis of retinal lipidome in bacterial endophthalmitis.Prostaglandins & other lipid mediators · 2024Review
- Distinct mouse models of Stargardt disease display differences in pharmacological targeting of ceramides and inflammatory responses.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- AAV-mediated base-editing therapy ameliorates the disease phenotypes in a mouse model of retinitis pigmentosa.Nature communications · 2023Article
- Ceramide compensation by ceramide synthases preserves retinal function and structure in a retinal dystrophy mouse model.Disease models & mechanisms · 2023Article
- rAAV-mediated over-expression of acid ceramidase prevents retinopathy in a mouse model of Farber lipogranulomatosis.Gene therapy · 2023Article
- Overcoming Treatment Challenges in Posterior Segment Diseases with Biodegradable Nano-Based Drug Delivery Systems.Pharmaceutics · 2023Review
- Solid Lipid Nanoparticles: Multitasking Nano-Carriers for Cancer Treatment.Pharmaceutics · 2023Review
- The Role of Ceramide in Inherited Retinal Disease Pathology.Advances in experimental medicine and biology · 2023Article
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
- Hydroxychloroquine Causes Early Inner Retinal Toxicity and Affects Autophagosome-Lysosomal Pathway and Sphingolipid Metabolism in the Retina.Molecular neurobiology · 2022Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
Retinitis pigmentosa (RP) is a genetic disease causing progressive apoptotic death of photoreceptors and, ultimately, incurable blindness. Using the retinal degeneration 10 (rd10) mouse model of RP, we investigated the role of ceramide, a proapoptotic sphingolipid, in retinal degeneration. We also tested the possibility that photoreceptor loss can be slowed or blocked by interfering with the ceramide signaling pathway of apoptosis in vivo. Retinal ceramide levels increased in rd10 mice during the period of maximum photoreceptor death. Single intraocular injections of myriocin, a powerful inhibitor of serine palmitoyl-CoA transferase, the rate-limiting enzyme of ceramide biosynthesis, lowered retinal ceramide levels to normal values and rescued photoreceptors from apoptotic death. Noninvasive treatment was achieved using eye drops consisting of a suspension of solid lipid nanoparticles loaded with myriocin. Short-term noninvasive treatment lowered retinal ceramide in a manner similar to intraocular injections, indicating that nanoparticles functioned as a vector permitting transcorneal drug administration. Prolonged treatment (10-20 d) with solid lipid nanoparticles increased photoreceptor survival, preserved photoreceptor morphology, and extended the ability of the retina to respond to light as assessed by electroretinography. In conclusion, pharmacological targeting of ceramide biosynthesis slowed the progression of RP in a mouse model, and therefore may represent a therapeutic approach to treating this disease in humans. Transcorneal administration of drugs carried in solid lipid nanoparticles, as experimented in this study, may facilitate continuous, noninvasive treatment of patients with RP and other retinal pathologies.
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