Salinomycin inhibits proliferative vitreoretinopathy formation in a mouse model

Autor: Alison Heffer, Ajay E. Kuriyan, Richard T. Libby, Victor Wang, Collynn F. Woeller, Steven E. Feldon
Rok vydání: 2020
Předmět:
0301 basic medicine
Proliferative vitreoretinopathy
Eye Diseases
Physiology
medicine.medical_treatment
Retinal Pigment Epithelium
Diagnostic Radiology
Mice
chemistry.chemical_compound
Medical Conditions
0302 clinical medicine
Immune Physiology
Medicine and Health Sciences
Tomography
Immune Response
CD20
Innate Immune System
Multidisciplinary
biology
Radiology and Imaging
Animal Models
Cytokine
medicine.anatomical_structure
Experimental Organism Systems
Intravitreal Injections
Medicine
Retinal Disorders
Cytokines
Immunohistochemistry
Female
Tumor necrosis factor alpha
Anatomy
Research Article
medicine.medical_specialty
Imaging Techniques
Science
Ocular Anatomy
CD3
Immunology
Mouse Models
Surgical and Invasive Medical Procedures
Research and Analysis Methods
Retina
03 medical and health sciences
Model Organisms
Signs and Symptoms
Ocular System
Diagnostic Medicine
Ophthalmology
medicine
Animals
Pyrans
Inflammation
Ionophores
business.industry
Vitreoretinopathy
Proliferative
Retinal Detachment
Biology and Life Sciences
Retinal
Molecular Development
medicine.disease
eye diseases
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
chemistry
Immune System
Animal Studies
030221 ophthalmology & optometry
biology.protein
Eyes
sense organs
Clinical Medicine
business
Head
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 15, Iss 12, p e0243626 (2020)
ISSN: 1932-6203
Popis: Proliferative vitreoretinopathy (PVR) is a progressive disease that develops in a subset of patients who undergo surgery for retinal detachment repair, and results in significant vision loss. PVR is characterized by the migration of retinal pigment epithelial (RPE) cells into the vitreous cavity, where they undergo epithelial-to-mesenchymal transition and form contractile membranes within the vitreous and along the retina, resulting in recurrent retinal detachments. Currently, surgical intervention is the only treatment for PVR and there are no pharmacological agents that effectively inhibit or prevent PVR formation. Here, we show that a single intravitreal injection of the polyether ionophore salinomycin (SNC) effectively inhibits the formation of PVR in a mouse model with no evidence of retinal toxicity. After 4 weeks, fundus photography and optical coherence tomography (OCT) demonstrated development of mean PVR grade of 3.5 (SD: 1.3) in mouse eyes injected with RPE cells/DMSO (vehicle), compared to mean PVR grade of 1.6 (SD: 1.3) in eyes injected with RPE cells/SNC (p = 0.001). Additionally, immunohistochemistry analysis showed RPE cells/SNC treatment reduced both fibrotic (αSMA, FN1, Vim) and inflammatory (GFAP, CD3, CD20) markers compared to control RPE cells/DMSO treatment. Finally, qPCR analysis confirmed that Tgfβ, Tnfα, Mcp1 (inflammatory/cytokine markers), and Fn1, Col1a1 and Acta2 (fibrotic markers) were significantly attenuated in the RPE cells/SNC group compared to RPE/DMSO control. These results suggest that SNC is a potential pharmacologic agent for the prevention of PVR in humans and warrants further investigation.
Databáze: OpenAIRE
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