ArticleThe American journal of pathology2016
Pharmacologic Activation of Wnt Signaling by Lithium Normalizes Retinal Vasculature in a Murine Model of Familial Exudative Vitreoretinopathy.
Article in The American journal of pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- Müller cell glutamine metabolism links photoreceptor and endothelial injury in diabetic retinopathy.Life science alliance · 2026Article
- The class A repeats of LRP5 are required for normal development of bone, retinal vasculature and mammary gland in vivo.Disease models & mechanisms · 2025Article
- Genetic Loss of RORα Impairs Visual Function With Rod Bipolar Cell Degeneration In Mice.Investigative ophthalmology & visual science · 2025Article
- Review
- Review
- Amino acid transporter SLC38A5 regulates developmental and pathological retinal angiogenesis.eLife · 2022Article
- Selective Activation of the Wnt-Signaling Pathway as a Novel Therapy for the Treatment of Diabetic Retinopathy and Other Retinal Vascular Diseases.Pharmaceutics · 2022Review
- GSK3 Is a Central Player in Retinal Degenerative Diseases but a Challenging Therapeutic Target.Cells · 2022Review
- Wnt/frizzled Signaling in Endothelium: A Major Player in Blood-Retinal- and Blood-Brain-Barrier Integrity.Cold Spring Harbor perspectives in medicine · 2022Review
- Article
- Structure and function of the retina of low-density lipoprotein receptor-related protein 5 (Lrp5)-deficient rats.Experimental eye research · 2022Article
- Lithium doped biphasic calcium phosphate: Structural analysis and osteo/odontogenic potentialFrontiers in bioengineering and biotechnology · 2022Article
- Wnt Signaling in Inner Blood-Retinal Barrier Maintenance.International journal of molecular sciences · 2021Review
- The neuroprotective role of Wnt signaling in the retina.Neural regeneration research · 2021Article
- Wnt signaling activates MFSD2A to suppress vascular endothelial transcytosis and maintain blood-retinal barrier.Science advances · 2020Article
- Wnt Activation After Inhibition Restores Trabecular Meshwork Cells Toward a Normal Phenotype.Investigative ophthalmology & visual science · 2020Article
- Review
- Protective Effects of Rapamycin on Trabecular Meshwork Cells in Glucocorticoid-Induced Glaucoma Mice.Frontiers in pharmacology · 2020Article
- Oxidative stress upregulates Wnt signaling in human retinal microvascular endothelial cells through activation of disheveled.Journal of cellular biochemistry · 2019Article
- Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation.Nature communications · 2019Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Familial exudative vitreoretinopathy (FEVR) is characterized by delayed retinal vascular development, which promotes hypoxia-induced pathologic vessels. In severe cases FEVR may lead to retinal detachment and visual impairment. Genetic studies linked FEVR with mutations in Wnt signaling ligand or receptors, including low-density lipoprotein receptor-related protein 5 (LRP5) gene. Here, we investigated ocular pathologies in a Lrp5 knockout (Lrp5(-/-)) mouse model of FEVR and explored whether treatment with a pharmacologic Wnt activator lithium could bypass the genetic defects, thereby protecting against eye pathologies. Lrp5(-/-) mice displayed significantly delayed retinal vascular development, absence of deep layer retinal vessels, leading to increased levels of vascular endothelial growth factor and subsequent pathologic glomeruloid vessels, as well as decreased inner retinal visual function. Lithium treatment in Lrp5(-/-) mice significantly restored the delayed development of retinal vasculature and the intralaminar capillary networks, suppressed formation of pathologic glomeruloid structures, and promoted hyaloid vessel regression. Moreover, lithium treatment partially rescued inner-retinal visual function and increased retinal thickness. These protective effects of lithium were largely mediated through restoration of canonical Wnt signaling in Lrp5(-/-) retina. Lithium treatment also substantially increased vascular tubular formation in LRP5-deficient endothelial cells. These findings suggest that pharmacologic activation of Wnt signaling may help treat ocular pathologies in FEVR and potentially other defective Wnt signaling-related diseases.
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