ArticleInvestigative ophthalmology & visual science2020
Suppression of cGMP-Dependent Photoreceptor Cytotoxicity With Mycophenolate Is Neuroprotective in Murine Models of Retinitis Pigmentosa.
Article in Investigative ophthalmology & visual science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- A human-specificMolecular therapy. Nucleic acids · 2025Article
- Retinopathy-associated inosine monophosphate dehydrogenase 1 mutations cause metabolic and filament defects in cones.Disease models & mechanisms · 2025Article
- Cyclic nucleotide signaling as a drug target in retinitis pigmentosa.FEBS letters · 2025Review
- Topical Administration of Novel FKBP12 Ligand MP-004 Improves Retinal Function and Structure in Retinitis Pigmentosa Models.Investigative ophthalmology & visual science · 2025Article
- The crossroads of ocular inflammation and inherited retinal degenerations: a report of two cases.Digital journal of ophthalmology : DJO · 2025Article
- Lower ratio of IMPDH1 to IMPDH2 sensitizes gliomas to chemotherapy.Cancer gene therapy · 2024Article
- Immunology of Retinitis Pigmentosa and Gene Therapy-Associated Uveitis.Cold Spring Harbor perspectives in medicine · 2024Review
- Molecular mechanisms underlying inherited photoreceptor degeneration as targets for therapeutic intervention.Frontiers in cellular neuroscience · 2024Review
- CRB1-Associated Retinal Dystrophy Patients Have Expanded Lewis Glycoantigen-Positive T Cells.Investigative ophthalmology & visual science · 2023Article
- C-subfamily ATP binding cassette transporters extrude the calcium fluorescent probe fluo-4 from a cone photoreceptor cell line.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- cGMP Signaling in Photoreceptor Degeneration.International journal of molecular sciences · 2023Review
- The double-edged sword of inflammation in inherited retinal degenerations: Clinical and preclinical evidence for mechanistically and prognostically impactful but treatable complications.Frontiers in cell and developmental biology · 2023Article
- Potential therapeutic strategies for photoreceptor degeneration: the path to restore vision.Journal of translational medicine · 2022Review
- Inherited Retinal Degeneration: PARP-Dependent Activation of Calpain Requires CNG Channel Activity.Biomolecules · 2022Article
- Programmed Non-Apoptotic Cell Death in Hereditary Retinal Degeneration: Crosstalk between cGMP-Dependent Pathways and PARthanatos?International journal of molecular sciences · 2021Review
- The role of cGMP-signalling and calcium-signalling in photoreceptor cell death: perspectives for therapy development.Pflugers Archiv : European journal of physiology · 2021Review
- Visual Side Effects Linked to Sildenafil Consumption: An Update.Biomedicines · 2021Review
- Clinical Perspective: Treating RPE65-Associated Retinal Dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- A Ketogenic & Low-Protein Diet Slows Retinal Degeneration in rd10 Mice.Translational vision science & technology · 2020Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Purpose: To determine the effect of mycophenolate mofetil (MMF) on retinal degeneration on two mouse models of retinitis pigmentosa. Methods: Intraperitoneal injections of MMF were administered daily in rd10 and c57 mice starting at postoperative day 12 (P12) and rd1 mice starting at P8. The effect of MMF was assessed with optical coherence tomography, immunohistochemistry, electroretinography, and OptoMotry. Whole retinal cyclic guanosine monophosphate (cGMP) and mycophenolic acid levels were quantified with mass spectrometry. Photoreceptor cGMP cytotoxicity was evaluated with cell counts of cGMP immunostaining. Results: MMF treatment significantly delays the onset of retinal degeneration and cGMP-dependent photoreceptor cytotoxicity in rd10 and rd1 mice, albeit a more modest effect in the latter. In rd10 mice, treatment with MMF showed robust preservation of the photoreceptors up to P22 with associated suppression of cGMP immunostaining and microglial activation; The neuroprotective effect diminished after P22, but outer retinal thickness was still significantly thicker by P35 and OptoMotry response was significantly better up to P60. Whereas cGMP immunostaining of the photoreceptors were present in rd10 and rd1 mice, hyperphysiological whole retinal cGMP levels were observed only in rd1 mice. Conclusions: Early treatment with MMF confers potent neuroprotection in two animal models of RP by suppressing the cGMP-dependent common pathway for photoreceptor cell death. The neuroprotective effect of MMF on cGMP-dependent cytotoxicity occurs independently of the presence of hyperphysiological whole retinal cGMP levels. Thus our data suggest that MMF may be an important new class of neuroprotective agent that could be useful in the treatment of patients with RP.
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